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Stefmnre  IGibrarg 


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FOCAL   INFECTION 


THE  LANE  MEDICAL  LECTURES 


BY 


FRANK  BILLINGS,  Sc.D.   (Harv.),  M.D. 


DELIVERED  ON  SEPTEMBER  20,   21,   22,   23  AND  24,   1915 

STANFORD    UNIVERSITY    MEDICAL   SCHOOL 

SAN   FRANCISCO,    CALIFORNIA 


D.   APPLETON  AND   COMPANY 

NEW  YORK  AND  LONDON 

1916 


i^-^icfr 


Copyright,  1916,  by 
D.  APPLETON  &  COMPANY 


T\C\\2- 

0, 


Printed  in  the  United  States  of  America 


INTRODUCTION 

The  importance  of  the  etiologic  relation  of  Focal  Infection 
to  Systemic  Diseases  has  been  a  subject  of  study  in  the  clinical 
material  of  Rush  Medical  College,  in  affiliation  with  the  Uni- 
versity of  Chicago  and  the  Presbyterian  Hospital  for  the  past 
twelve  or  more  years. 

As  the  study  progressed,  the  attention  and  cooperation  of 
clinicians  and  laboratory  workers  were  aroused  and  developed 
into  a  scheme  of  "team  work."  This  esprit  de  corps  eventually 
embraced  the  nursing  staff  and  the  patients.  Real  clinical  re- 
search was  made  possible  by  this  cooperative  spirit.  Living 
morbid  tissues  were  obtained  at  surgical  operations  and  also 
from  other  patients,  who  submitted  voluntarily  and  in  many 
instances  requested  the  removal,  when  necessary  under  local  or 
general  gas  anesthesia,  of  bits  of  infected  tissue  (muscle, 
capsule  of  joints,  lymph  nodes,  erythematous  nodes,  fibrous 
nodes  of  tendons)  of  exudates  and  of  the  blood,  for  experimental 
purposes. 

Histologic  and  bacteriologic  studies  of  this  material  were 
made.  Animal  inoculation  was  carried  on  and  the  lesions  of 
the  experimental  animals  were  studied  and  compared  with  the 
morbid  human  tissues  which  were  the  source  of  the  investi- 
gation. 

Eventually  the  Memorial  Institute  for  Infectious  Diseases, 
the  Otho  S.  A.  Sprague  Memorial  Institute  and  the  Pathological 
and  Research  Department  of  St.  Luke's  Free  Hospital  of  Chi- 
cago cooperated  in  the  work. 

The  conclusions  based  upon  the  research  were  not  made  until 
a  critical  survey  of  the  work  and  the  results  were  investigated 

T 


vi  INTRODUCTION 

by  other  qualified  clinicians,  pathologists  and  research  workers. 

I  may  not  name,  because  of  want  of  space,  all  who  have  co- 
operated in  the  team  work,  which  has  made  the  research  a 
practical  success  and  has  opened  up  a  broad  field  for  a  more 
extended  study  along  similar  lines.  To  my  clinical  colleagues 
in  the  college  and  hospital  I  extend  my  grateful  thanks.  Pro- 
fessors L.  Hektoen,  E.  R.  LeCount  and  H.  Gideon  Wells  have 
been  of  invaluable  aid  to  all  of  us,  with  advice  always  helpful 
though  sometimes  critical.  The  members  of  the  house  staff 
have  rendered  invaluable  help  by  a  tireless  and  enthusiastic 
bedside  and  clinical  laboratory  service.  Many  of  these 
internes  have  continued  in  the  work  as  clinicians,  patholo- 
gists and  clinical  bacteriologists.  Drs.  D.  J.  Davis,  R.  T. 
Woodyatt,  H.  K.  Nicoll,  W.  E.  Post,  E.  E.  Irons,  A.  M. 
Moody,  F.  W.  Gaarde,  J.  J.  Moore,  and  George  H.  Coleman 
have  done  notable  work  in  bacteriology,  chemistry,  and  in 
experiments  upon  animals. 

The  broad  significance  of  the  relation  of  focal  infection  to 
systemic  disease  has  been  made  more  definite  by  the  brilliant 
work  of  Edward  C.  Rosenow,  who  joined  the  clinic  in  1904. 

These  lectures,  therefore,  represent  the  cooperative  study  of 
many  workers.  I  have  made  free  use  of  the  results  of  the 
labors  of  all  who  have  aided  in  the  work  and  I  am  proud  to  be 
their  spokesman. 

Frank  Billings. 


CONTENTS 

lecture;  page 

I.     A  General  Consideration  of  Focal  Infection    .     •  1 

Site  of  Primary  Foci — Etiology  of  Focal  Infection — 
Susceptibility  to  Systemic  and  Local  Diseases  from  the 
Focus  of  Infection — Greater  Susceptibility  to  Systemic 
Disease  from  a  Focal  Infection  Undoubtedly  Occurs — 
The  Diagnosis  of  the  Focus  of  Infection — Mode  of 
Dissemination  of  Bacteria  and  Toxic  Products  from 
the  Focus  of  Infection — Focal  Infection  and  Anaphy- 
laxis. 

II.  The  Streptococcus-pneumococcus  Group.  Trans- 
mutability  of  the  Members  Thereof.  Patho- 
genicity and  Specific  Tissue  Affinity  of  Trans- 
mutation Forms 26 

Transmutation  Within  the  Members  of  the  Strepto- 
coccus-Pneumococcus   Group. 

III.     Acute  Diseases  Related  to  Focal  Infection  ...       48 

Acute  Rheumatic  Fever — Rheumatic  Endocarditis, 
Myocarditis  and  Pericarditis — Chorea — Acute  Sys- 
temic Gonococcus  Infection — Malignant  Endocardi- 
tis— Acute  Nephritis — Acute  Appendicitis — Cholecys- 
titis— Acute  Gastric  and  Duodenal  Ulcer — Acute  Pan- 
creatitis— Erythema  Nodosum  Herpes — Spinal  Mye- 
litis— Acute     Osteomyelitis — Thyroiditis — Iridocyclitis. 

IV.     Chronic  Diseases  Related  to  Focal  Infection    .     .      107 

Chronic  Infectious  Arthritis — Chronic  Infectious  Ne- 
phritis— Chronic  Cholecystitis — Chronic  Peptic  Ul- 
cer— Chronic   Infectious    Endocarditis. 

vii 


viii  CONTENTS 

LECTURE  PAGE 

V.     Treatment 127 

Focal  Infection — Treatment  of  Resulting  Acute  and 
Chronic  Systemic  Diseases — Serum  and  Vaccine  Ther- 
apy. 

Bibliography ...     159 


LIST  OF  ILLUSTRATIONS 

FIG.  PAGE 

1.  Strain  595  as  a  hemolytic  streptococcus  isolated  from  a 

case  of   scarlet  fever 28 

2.  Strain   595   as  streptococcus  viridans         29 

3.  Strain  595   as  a  pneumococcus 29 

4.  Strain  of  streptococcus    from   rheumatism 30 

5.  The  same  strain  as  in  Fig.  4  after  it  was  transformed 

into    a    pneumococcus  J 31 

6.  Highly  virulent  pneumococcus 31 

7.  Same  strain  as  in  Fig.  6  after  transformation  into  hem- 

olytic streptococcus 32 

8.  Streptococcus,  nodular,  valvular  and  mural  endocarditis 

of  dog 53 

9.  Vegetative   and  ulcerative   endocarditis   of  aortic  valves 

and  aorta  of  dog 60 

10.  Section  through  vegetations   on   mitral  valve   shown   in 

Fig.   9     •     •     • 61 

11.  A  glomerulus  containing  a  hyaline  thrombus     ....  63 

12.  Masses  of  fibrin  in  a  glomerulus 64 

13.  A  glomerulus  in  which  are  masses  of  cocci  filling  a  group 

of  capillaries 65 

14.  Marked  hemorrhage  of  the  appendix 67 

15.  Hemorrhage    and   localized   infection   of    mucous   mem- 

brane         68 

16.  Human  appendicitis  12  hours  after  onset  in  young  man  69 

17.  Diplococci  in  peritoneal  coat  of  appendix 70 

18.  Hemorrhage  necrosis  and  leukocytic  infiltration  ...  71 
19-  Streptococci  in  lymph  follicle  shown  in  Fig.  18  .  72 
20.      Streptococci  and  fusiform  bacilli  in  human  gangrenous 

appendicitis 72 

ix 


x  LIST  OF  ILLUSTRATIONS 

FIQ.  PAGB 

21.  Hemorrhage,  necrosis  and  leukocytic  infiltration  of  ap- 

pendix  24  hours  after  infection 73 

22.  Streptococci  and  fusiform  bacilli  of  appendix  of  rabbit       73 

23.  Photomicrograph  of  24-hour  culture  in  ascites-dextrose- 

broth  of  a  streptococcus 74 

24.  Hemorrhagic  cholecystitis  in  dog    ........  75 

25.  Marked  edema  of  gall-bladder  in  dog 76 

26.  Streptococci  in  lymph  space  of  edematous  wall  of  gall- 

bladder shown  in  Fig.  25 77 

27.  Photomicrograph  of  24-hour  ascites-dextrose-broth  cul- 

ture of  streptococcus  from  human  ulcer 78 

28.  Marked  ulceration  of  stomach  in  guinea  pig    ....       79 
29-     Photomicrograph   24-hour  ascites-dextrose-broth  culture 

of  a  streptococcus  from  blind  abscess  of  jaw    ...       79 

30.  Ulcer  of  stomach  of  dog 80 

31.  Capillary   filled   with   diplococci  in  the  apex   of  ulcer  , 

shown  in  Fig.  30 80 

32.  Section  of  wall  of  stomach  of  rabbit 81 

33.  Streptococci   at   apex   of   wedge-shaped   area   shown   in 

Fig.  32 82 

34.  Hemorrhagic  pancreatitis  in  dog 83 

35.  Section  of  pancreas  in  dog 84 

36.  Photomicrograph   showing   diplococci   in  area  of  round 

cell    infiltration 85 

37.  Subcutaneous  tissues  from  erythema  nodosum  in  man    .  86 

38.  Subcutaneous  tissue  from  erythema  nodosum  in  man    .  87 

39.  Smear  from  single  colony  in  ascites-dextrose-agar     .     .  87 

40.  Smear  from  blood  of  guinea  pig 88 

41.  Photograph   showing   circumscribed  hemorrhages  of  the 

skin  and   symmetrical  hemorrhages  of  the  fascia  of 

the  inner  aspect  of  the  legs  of.  a  rabbit 89 

42.  Section  of  skin  of  rabbit  showing  hemorrhage  and  leu- 

kocytic  and   round   cell   infiltration   of   subcutaneous 
tissue 90 

43.  A  diplococcus  in  the  area  of  infiltration  shown  in  Fig.  42       91 


LIST  OF  ILLUSTRATIONS  xi 

fig.  PAGB 

44.  Section   of   the   artery    from    the   area   of  subcutaneous 

hemorrhage 91 

45.  Diplobacilli  in  the  wall  of  artery  shown  in  Fig.  44    .      .        92 

46.  Photomicrograph  of  24-hour  culture  in  ascites-dextrose- 

broth  of   a  streptococcus  from   the  spinal   fluid  of  a 
rabbit 92 

47.  Herpes  as  seen  on  under  surface  of  the  skin  over  the 

lower  right  thoracic  region  of  a  rabbit 93 

48.  Diplococci  in  the  hemorrhagic  spinal  ganglion  ....        94 

49-      Herpes  of  the   skin  of  the  inner   and  upper   aspect  of 

right  thigh  of  a  rabbit 95 

50.  Thrombosis  of  a  vein   (a)   and  paravascular  infiltration 

(b)    of  the   posterior  spinal  root 96 

51.  Diplococci  in  leukocytes  within  a  thrombosed  vein    .     .       97 

52.  Diplococci  in  hemorrhagic  and  infiltrated  area  shown  in 

Fig.  53 97 

53.  Marked  hemorrhage   (a)   and  leukocytic  infiltration   (b) 

surrounding  the  lumbar  nerve 98 

54.  Herpes   of  tongue,  mucous   membrane  about  teeth   and 

lips  of  rabbit 99 

55.  Herpes  of  skin  of  left  side  of  face  of  rabbit   ....      100 

56.  Hemorrhage   (a)   and  round  cell  infiltration   (b)  of  the 

gasserian   ganglion  of   dog 101 

57.  Section  of  iris  and  ciliary  body  of  rabbit 104 

58.  Photomicrograph  of  streptococci  in  area  of  infiltration 

shown    in    Fig.    57 105 

59.  Localized  hemorrhages  (a)  in  the  sclera  near  the  limbus 

and  at  the  attachment  of  the  external  rectus  muscle 

of   rabbit 106 

60.  Diplococcus  adjacent  to  area  of  hemorrhage  in  Fig.  59  .      106 

61.  A  typical  subacute  focal  lesion  in  the  cortex    .      .      .      .      114 

62.  An    interlobular    vein    surrounded   by   lymphocytes    and 

plasma   cells 115 

63.  Cholecystitis  and  cholelithiasis  in  dog 117 


xii  LIST  OF  ILLUSTRATIONS 

FIG.  PAGE 

64.  Streptococci    and    leukocytic    infiltration    in    peritoneal 

coat  in  perforating  ulcer  of  the  stomach  of  man  .     .     118 

65.  Streptococci  in  peritoneal  coat  of  ulcer  of  stomach  in 

rabbit 119 

66.  Streptococci  and  leukocytic  infiltration  in  chronic  ulcer 

of  man 119 

67.  Chronic  ulcer   of   duodenum   of  dog   13   weeks    after   a 

single    intravenous    injection    of    streptococcus    from 
ulcer  of  the  duodenum  of  man 120 

68.  Chronic   ulcer   of   duodenum   of   dog    13   weeks   after   a 

single    intravenous    injection    of    streptococcus    from 
human  ulcer 120 


FOCAL  INFECTION 


FOCAL   INFECTION 

LECTURE  I 

A  GENERAL   CONSIDERATION   OF   FOCAL   INFECTION 

Permit  me  to  express  to  you  my  sincere  appreciation 
of  the  honor  conferred  upon  me,  by  the  Trustees  and 
Faculty  of  Stanford  University  Medical  School,  to 
give  the  fifteenth  course  of  the  Lane  Medical  Lectures. 

I  am  complimented  also  by  the  fact  that  the  group 
of  workers  with  whom  I  am  associated,  has  been  en- 
gaged in  the  clinical  and  laboratory  investigation  of  a 
subject  about  which  you  desire  to  hear. 

Systemic  or  general  disease  due  to  a  local  infection  is 
a  conception  as  old  as  medical  knowledge. 

Long  before  the  development  of  bacteriology  there 
had  been  noted  many  examples  of  general  disease  aris- 
ing from  trivial  and  serious  accidental  and  surgical 
wounds.  The  general  disease  was,  as  a  rule,  character- 
ized by  chills,  fever,  and  general  debility  and  was  often 
fatal. 

The  cause  was  thought  to  be  contamination  of  the 
wound  or  focus  with  some  substance  which  caused  putre- 
faction. Hence  the  resulting  general  disease  was  called 
septic.     The  so-called  laudable  pus  of  an  uneventful 

healing  wound,  when  contaminated  with  putrefactive 

1 


2  FOCAL  INFECTION 

poison,  which  changed  in  color,  fermented,  acquired  a 
bad  odor,  and,  gaining  entrance  to  the  blood  stream, 
caused  pyemia  or  septicopyemia.  Discussion  as  to  the 
origin  of  the  putrefactive  agents  brought  forth  many 
theories  until  the  epoch-making  discovery  of  Semmel- 
weis  ( 1847)  who  traced  the  constant  prevalence  of  child- 
bed fever  in  the  Vienna  lying-in  hospital  to  contamina- 
tion of  the  genitalia  of  the  woman  in  labor  by  the  un- 
clean hands  of  students  and  physicians  fresh  from  the 
dissecting  rooms.  Cadaveric  poison,  therefore,  was 
proved  to  be  a  cause  of  childbed  sepsis.  Local  infection 
followed  by  embolism,  thrombosis  and  septicemia  were 
recognized  as  successive  stages  which  were  observed  in 
surgical  and  obstetrical  sepsis.  E.  Klebs  was  probably 
the  first  to  recognize  that  local  and  general  sepsis  were 
due  to  microorganisms  which  he  termed  microsporon 
septicum.  But  no  material  gain  in  practical  results  oc- 
curred until  the  deductions  of  Lister,  based  upon  the 
brilliant  researches  of  Pasteur,  that  wound  infection  was 
due  to  a  virus  animatum  and  the  rational  application  by 
Lister  of  measures  to  prevent  wound  infection.  Lister- 
ism — antiseptic  surgery — was  of  rapid  growth  and  in  its 
evolutional  form  as  applied  today  makes  general  sepsis 
in  surgery  and  midwifery  a  criminal  offense  due  to  ig- 
norance, carelessness  or  faulty  technic. 

But  focal  infection,  which  is  the  subject  of  these  lec- 
tures, is  broader  in  its  application  than  is  expressed  in 
surgical  sepsis. 

During  the  last  decade  a  new  interest  has  been 
aroused  in  the  subject  of  focal  infection  as  an  etiologic 
factor  of  local  and  of  general  diseases.    The  wider  dis- 


A  GENERAL  CONSIDERATION  3 

cussion  of  the  subject  made  it  appear  as  a  new  prin- 
ciple. The  wider  and  broader  interest  in  the  subject 
has  been  brought  about  by  a  better  knowledge  of  bac- 
teriology, of  modes  of  infection,  and  by  cooperative  lab- 
oratory and  clinical  research. 

\A.  focus  of  infection  may  be  defined  as  a  circum- 
scribed area  of  tissue  infected  with  pathogenic  micro- 
organisms. Foci  of  infection  may  be  primary  and  sec- 
ondary. Primary  foci  usually  are  located  in  tissues 
communicating  with  a  mucous  or  cutaneous  surface. 
Secondary  foci  are  the  direct  results  of  infection  from 
other  foci  through  contiguous  tissues  or  at  a  distance 
through  the  blood  stream  or  lymph  channels. 

SITE   OF   PRIMARY   FOCI 

Primary  foci  of  infection  may  be  located  anywhere 
in  the  body.  Infection  of  the  teeth  and  jaws,  with  the 
especial  development  of  pyorrhea  dentalis  and  alveolar 
abscess,  infection  of  the  faucial  and  nasopharyngeal 
tonsils  and  of  the  mastoid,  the  maxillary  and  other 
accessory  sinuses  are  the  most  common  forms  of 
focal  infection.  Submucous  and  subcutaneous  abscesses 
including  the  finger  and  toe  nails  are  occasional  foci. 
Chronic  infection  of  the  bronchi  and  bronchiectasis; 
chronic  infection  of  the  gastro-intestinal  tract  and  aux- 
iliary organs  of  digestion,  including  cholecystitis,  ap- 
pendicitis, intestinal  ulcers  and  intestinal  stasis  due  to 
morbid  anatomical  conditions;  chronic  infection  of  the 
genito-urinary  tract,  including  metritis,  salpingitis, 
vesiculitis  seminalis,  prostatitis,  cystitis  and  pyelitis,  are 
not  uncommon  forms.    Infected  lymph  nodes,  which  are 


4  FOCAL  INFECTION 

secondary  to  the  primary  foci  named,  become  additional 
depots  of  local  infection.  The  secondary  lymph  node 
infection  may  persist  after  the  etiologic,  distal,  primary 
focus  has  been  removed  or  has  spontaneously  disap- 
peared. Other  secondary  foci  may  appear  in  various 
tissues  as  a  part  of  the  general  or  local  disease  which 
results  from  a  primary  focus.  As  we  shall  see,  systemic 
and  local  disease  may  occur  through  infection  from  a 
focal  point  by  way  of  the  blood  stream.  This  mode  of 
infection  is  often  embolic  in  character.  The  tissues  so 
infected  may  constitute  new  foci,  which  in  part  explains 
the  chronicity  of  many  local  and  general  infections. 

ETIOLOGY  OF  FOCAL  INFECTIONS 

Focal  infection  especially  of  the  structures  of  the 
mouth  and  the  upper  air  passages  is  a  very  prevalent 
condition.  The  incidence  of  infection  of  the  mouth 
is  enormous  everywhere.  In  addition  to  the  presence  of 
innumerable  saprophytes  in  the  mouth  and  pharynx, 
one  may  find  in  the  saliva  and  pharyngeal  mucus,  strep- 
tococci and  staphylococci,  micrococcus  catarrhalis,  pneu- 
mococci,  diphtheria  and  pseudodiphtheria  bacilli,  men- 
ingococci, tubercle  bacilli  and  many  other  pathogenic 
bacteria.  C.  C.  Bass  ( 1 )  and  others  state  that  endameba 
buccalis  was  found  in  the  mouths  of  95  and  even  100 
per  cent,  of  all  adults  examined.  The  presence  of  these 
infectious  microorganisms  in  the  mouth  and  upper  res- 
piratory tract  indicates  unhealthful  surroundings  and 
individual  uncleanliness.  The  individual  carrier  infects 
others  by  contact  and  by  other  means. 


A  GENERAL  CONSIDERATION  5 

The  character  of  local  infection  in  various  parts  of  the 
body  is  so  important  that  separate  consideration  must 
be  given  to  each  kind. 

Pyorrhea  D entails  and  Alveolar  Abscess 

Pyorrhea  dentalis  and  alveolar  abscess  (Rigg's  dis- 
ease) is  a  condition  incident  to  all  classes  of  adults.  It 
is  much  less  prevalent  in  the  young.  It  is  a  disease 
which  fundamentally  involves  the  periosteum  of  the  root 
and  neck  of  the  tooth  (peridental  membrane) .  It  is  the 
chief  cause  of  the  loss  of  the  permanent  teeth.  It  may  be 
associated  with  caries  of  the  crown,  and,  on  the  Other 
hand,  the  crown  may  remain  normal.  The  infection 
first  attacks  the  edges  of  the  gum,  which  may  be  macer- 
ated by  decaying  food  particles  between  the  teeth,  or 
the  gum  may  be  injured  in  masticating  hard  substances, 
by  toothpicks,  and  other  traumatic  agents.  Ill  health 
and  poor  general  nutrition  make  the  gums  less  resistant. 
The  endameba  buccalis  and  various  pyogenic  bacteria 
which  gain  admission  to  the  edges  of  the  gums  cause 
retraction  of  the  soft  tissues  and  the  exposed  peridental 
membrane  of  the  neck  and  root  of  the  tooth  become  in- 
volved in  sequence.  This  periosteum  injured  or  de- 
stroyed, there  follows  softening  and  ulceration  of  the 
soft  parts  with  the  end  result  of  acute  or  chronic  alveo- 
lar abscess. 

Endameba  has  been  known  to  be  a  parasite  of  the 
mouth  for  many  years.  Its  relation  to  pyorrhea  alveo- 
laris  was  first  described  by  F.  M.  Barrett,  (2)  in  col- 
laboration with  Allen  J.  Smith  in  1914.  Without  a 
knowledge  of  the  work  of  Barrett  and  Smith,  C.  C. 


6  FOCAL  INFECTION 

Bass  and  F.  M.  Johns  (1)  had  recognized  the  relation 
of  the  parasite  to  pyorrhea  and  had  begun  experimental 
treatment  with  emetin.  The  endamebas  may  be  found 
in  the  gum  lesions  and  they  are  numerous  in  the  deeper 
abscesses  where  they  live  on  the  dead  tissues.  Bass  and 
other  investigators  believe  that  the  endameba  buccalis 
is  the  chief  etiologic  factor  in  the  development  of  pyor- 
rhea alveolaris. 

From  the  pus  and  dead  material  of  alveolar  abscess 
and  the  infected  pulp  of  the  teeth,  with  a  proper  technic, 
cultures  yield  streptococci,  chiefly  streptococcus  viridans 
and  streptococcus  hemolyticus,  staphylococcus  aureus 
and  albus,  fusiform  bacilli  and  other  less  important  bac- 
teria. Doubtless  the  endamebas  play  an  important  part 
in  the  occurrence  of  pyorrhea  alveolaris  and  permit  in- 
fection with  the  pyogenic  bacteria.  The  bacteria  pres- 
ent in  the  infected  areas  are  the  important  factors,  how- 
ever, in  the  causation  of  general  infection  from  the 
focus. 

Acute  and  Chronic  Tonsillitis  and  Infection  of 
Lymphoid  Tissue  in  the  Nasopharynx 

The  faucial  tonsils  are  frequently  infected  through 
contaminated  air,  infected  food,  especially  milk,  and  by 
direct  contact  with  infected  individuals.  Many  children 
have  large  tonsils  and  overgrowth  of  other  lymphoid 
structures  of  the  pharynx  which  make  a  good  soil  for 
bacterial  growth.  Hypertrophy  of  the  tonsils  and  ade- 
noid overgrowth  in  the  nasopharynx  interfere  with  res- 
piration, resulting  in  deformities  of  the  bones  of  the  face 
and  thorax.    Obstruction  of  the  upper  air  passages  pre- 


A  GENERAL  CONSIDERATION  7 

vents  proper  drainage  from  the  nasal  cavities  and  ac- 
cessory sinuses  and  leads  to  infection  of  the  middle  ear, 
the  sinuses  of  the  head  and  the  mucous  membrane  cover- 
ing the  turbinate  bodies.  In  adult  life  small  faucial  ton- 
sils may  look  innocent  because  of  a  smooth  covering  of 
mucous  membrane  which  seals  over  infected  crypts  or 
an  actual  abscess.  So,  too,  the  stumps  of  tonsils,  the 
remains  of  tonsillotomy,  may  contain  infected  crypts 
sealed  by  the  operative  scar. 

Infected  tonsils  and  adenoids  may  yield  cultures  of 
streptococcus  mucosus,  streptococcus  viridans,  strepto- 
coccus hemolysans,  micrococcus  catarrhalis,  pneumococ- 
ci,  bacillus  mucosus  capsulatus,  grippe  bacillus,  diph- 
theria and  pseudodiphtheria  bacilli  and  other  pathogenic 
microorganisms.  The  tonsils  and  surrounding  lymph 
tissues  may  be  a  focus  of  tuberculosis  from  which  lymph 
nodes  of  the  neck  and  mediastinum  may  become  in- 
fected. Smith  and  Barrett  (3)  found  endameba  buc- 
calis  in  the  tonsils  of  five  of  seventeen  patients.  The 
presence  of  endamebas  in  the  tonsils  would  probably 
favor  deep  pyogenic  infection. 

Mastoiditis  and  Sinusitis  of  the  Maxillary  and  Other 
Accessory  Sinuses 

Mastoiditis  as  an  extension  of  nasopharyngeal  infec- 
tion through  the  eustachian  tube  and  middle  ear  is  a 
serious  and  frequent  disease  of  the  young  and  occasion- 
ally of  adults.  Members  of  the  streptococcus-pneumo- 
coccus  group  are  the  usual  infectious  agents.  Staphylo- 
cocci and  influenza  bacilli  may  be  the  invaders.  The 
proximity  of  the  mastoid  cells  to  the  venous  sinuses  of 


8  FOCAL  INFECTION 

the  skull  makes  this  focus  a  frequent  source  of  sinus 
thrombosis,  bacteriemia  and  meningitis. 

Infection  of  the  accessory  sinuses  is  of  frequent  oc- 
currence during  the  changeable  seasons.  The  most  fre- 
quent bacterial  causes  are  strains  of  streptococci,  pneu- 
mococci,  micrococcus  catarrhalis  and  influenza  bacilli — 
less  frequently  staphylococci.  In  chronic  sinusitis,  often 
unrecognized,  various  pyogenic  bacteria  occur  with  the 
occasional  presence  of  colon  bacilli,  the  bacillus  welchii 
and  various  saprophytic  organisms.  Sinus  infection  is 
frequently  chronic  because  of  faulty  drainage.  When 
chronic  it  may  present  local  symptoms  only  when  a  new 
"cold"  is  acquired. 

All  infectious  foci  of  the  head  may  be  associated  with 
secondary  infection  of  the  lymph  nodes  of  the  neck  and 
mediastinum.  Kretz  (25)  records  six  hundred  autop- 
sies with  especial  reference  to  the  infection  of  the  cer- 
vical lymph  nodes.  In  childhood,  he  says,  the  superfi- 
cial nodes  of  the  anterior  triangles  are  involved  and  soft, 
while  in  adults  the  deeper  glands  at  the  angle  of  the  jaw 
and  the  region  of  the  internal  jugular  vein  are  more 
often  involved  and  are  usually  indurated.  He  stated 
that  in  90  per  cent,  of  the  bodies  examined  the  glands 
showed  streptococcus  infection  and  10  per  cent,  yielded 
other  bacteria.  Kretz  believes  that  many  children  suffer 
from  acute  glandular  fever,  due  to  angina,  and  that  the 
infectious  microorganisms  pass  rapidly  through  the 
cervical  lymph  channels  and  glands  with  resulting  severe 
bacteriemia  and  fever.  Hence  a  fatal  result  obtains  in 
virulent  types  of  glandular  fever  in  children.  He  states 
that  in  older  people  the  filtration  through  the  deeper 


A  GENERAL  CONSIDERATION  9 

cervical  glands  is  slower.  Consequently  the  virulence 
of  the  bacteria  and  the  degree  of  bacteriemia  may  be 
less.  The  lymph  node  infection  may  disappear  with 
the  removal  of  the  primary  focus  or  may  persist  actively 
as  new  foci  in  the  production  of  systemic  disease  or  the 
infection  of  the  nodes  may  become  permanently  latent. 

Chronic  Bronchitis  and  Bronchiectasis 

Long  standing  bronchitis  associated  with  emphysema, 
asthma,  and  bronchiectatic  cavities  presents  a  type  of 
localized  chronic  infection  which  may  be  an  etiologic  fac- 
tor in  systemic  infection  and  trophometabolic  changes 
in  bones  and  joints  probably  due  to  toxic  products  ab- 
sorbed from  the  site  of  infection.  The  sputa  in  the 
conditions  named  yield  cultures  of  many  saprophytic 
bacteria  as  well  as  streptococci,  staphylococci,  pneumo- 
cocci,  influenza  bacilli,  micrococcus  catarrhalis,  fusi- 
form anaerobes  and  other  pathogenic  bacteria. 

Focal  Infection  of  the  Gastro-intestinal  Canal,  Vermi- 
form Appendix,  Gall-bladder  and  Pancreas 

Auto-infection  and  auto-intoxication  from  the  intes- 
tinal canal  as  a  cause  of  disease  is  a  popular  idea  with 
the  medical  profession.  Stasis  of  the  intestinal  contents 
is  alleged  to  be  an  important  factor  in  the  causation 
of  auto-infection.  Intestinal  stasis  may  be  due  to  habit- 
ual constipation,  to  partial  obstruction  of  the  intestines 
due  to  congenital  defects,  or  to  acquired  morbid  ana- 
tomical conditions  which  favor  the  presence  of  patho- 
genic bacteria  with  putrefactive  changes,  resulting,  it  is 
believed  by  many,  in  toxemia  and  systemic  disease.    An- 


10  FOCAL  INFECTION 

emia,  chronic  arthritis,  Bright's  disease,  arteriosclerosis, 
and  even  local  diseases  like  appendicitis,  cholecystitis 
calculosa  and  peptic  ulcer,  are  believed  to  be  caused  by- 
stasis  and  putrefactive  changes  in  the  intestinal  con- 
tents. This  large  focus  of  infection  has  been  attacked 
in  the  attempt  to  remove  the  offending  bacteria  by  intes- 
tinal antiseptics,  colonic  flushing,  buttermilk  and  other 
lactic  acid  bacilli  containing  fluids  and  tablets  and  ca- 
thartic waters,  and  the  surgeon  has  invaded  the  abdomen 
to  correct  the  intestinal  stasis  by  removing  kinks,  veils 
and  other  alleged  deformities,  and  even  by  resecting  the 
entire  colon. 

There  is  doubtless  some  truth  in  the  theory  of  in- 
testinal infection,  but  the  pathogenic  microorganisms  in 
the  intestinal  canal,  which  remain  there  as  infectious  or- 
ganisms, gain  entrance  chiefly  by  swallowing  infectious 
material  from  the  mouth,  throat  and  nose  and  also 
through  infected  food  and  drink,  especially  milk,  for 
milk  is  very  apt  to  contain  streptococci  which  are  viru- 
lent or  may  become  so.  Streptococci  and  other  patho- 
genic bacteria  probably  infect  the  lymph  tissue  of  the 
intestine  or  may  pass  into  the  lymph  nodes  of  the  mes- 
entery and  set  up  active  or  passive  infection.  As  we 
shall  see  later,  streptococcal  infection  from  a  focus  in 
the  head  may  hematogenously  cause  appendicitis,  chole- 
cystitis, peptic  ulcer  and  pancreatitis.  In  addition  to 
the  immediate  local  damage,  the  bacteria  in  these  tissues 
may  form  new  foci  from  which  proximal  lymph  nodes 
may  become  infected.  From  these  new  foci  further  ex- 
tension of  the  infection  may  take  place  through  the 
lymph  channels  or  the  blood  stream  or  through  both. 


A  GENERAL  CONSIDERATION         11 

Appendicitis  is  usually  caused  by  a  strain  of  the 
streptococcus  group  from  a  mouth  or  throat  focus.  The 
colon  bacilli  and  other  members  of  the  intestinal  bac- 
terial flora  in  the  appendix  may  take  on  pathogenic 
qualities  and  cause  a  mixed  infection.  Often  this  mixed 
infection  is  fulminating  and  severe.  Chronic  types  of 
appendicitis  not  only  cause  local  distress  and  digestive 
disturbances,  but  may  become  a  cause  of  infection  of 
the  mesenteric  glands  and  through  the  lymph  vessels 
and  blood  stream  may  infect  the  liver,  bile  tracts,  and 
subdiaphragmatic  tissues.  Cholecystitis  may  also  be 
caused  by  a  streptococcus  infection  from  a  focus  of  the 
head.  The  infectious  microorganism  carried  in  the 
blood  stream  from  the  focus  may  lodge  in  the  terminal 
blood  vessels  of  the  fundus  of  the  gall-bladder.  The 
inoculated  blood  vessel  becomes  wholly  or  partly  oc- 
cluded by  endothelial  proliferation  and  leukocytic  infil- 
tration, and  blood  containing  the  bacteria  escapes  into 
the  wall  of  the  bladder.  Necrosis  of  the  local  tissues 
and  rupture  of  the  infected  material  into  the  gall-blad- 
der may  occur.  Acute  severe  cholecystitis  may  result. 
Less  severe  infection  may  result  in  a  chronic  cholecysti- 
tis and  subsequent  gall-stone  formation.  Typhoid  and 
colon  bacilli  may  cause  cholecystitis  or  may  be  associated 
in  a  mixed  infection  of  the  organ.  Cholecystitis  may. 
be  a  focus  of  systemic  infection. 

The  rectum,  with  its  rich  supply  of  hemorrhoidal 
veins,  becomes  a  focus  of  infection,  through  ulcers,  in- 
fected thrombi  in  veins  and  local  abscesses.  Infected 
thrombi  from  these  points  may  produce  acute  circum- 
scribed hepatitis  (abscess),  and  bacteriemia. 


12  FOCAL  INFECTION 

Foci  of  Infection  of  the  Genito-urinary  Tract 

Immediately  after  childbirth,  miscarriage  or  abortion, 
the  endometrium  is  very  susceptible  to  infection  by  any 
of  the  pyogenic  microorganisms.  The  resulting  focus 
is  usually  serious  because  of  the  tendency  to  the  forma- 
tion of  infected  thrombi  in  the  uterine  sinuses.  The 
bacteriemia  which  results  is  severe.  At  other  times 
the  endometrium  is  not  a  frequent  site  of  focal  infection. 

The  fallopian  tubes  are  very  susceptible  to  infection 
with  pyogenic  bacteria,  but  most  frequently  the  cause 
is  the  gonococcus  with  resulting  obliterating  salpingitis 
or  abscess  which  may  infect  the  peritoneum.  Tubercu- 
lous salpingitis  may  cause  tuberculous  peritonitis.  Fo- 
cal infection  in  the  form  of  gonorrheal  vaginitis  is  a 
common  disease  of  defective  girls  and  of  girls  in  hospi- 
tals and  public  institutions.  The  condition  is  important 
because  of  the  readiness  with  which  it  is  conveyed  from 
individual  to  individual  by  contact  or  through  fomites. 
The  condition  usually  remains  a  local  one  with  conse- 
quent discomfort  confined  to  the  parts  involved.  Oc- 
casionally the  peritoneum,  joints  and  other  tissues  may 
become  infected  from  the  vaginal,  uterine  and  tubal 
focus. 

The  seminal  vesicles  and  testes  are  sites  of  focal  in- 
fection with  the  gonococcus,  tubercle  bacillus  and  pyo- 
genic bacteria. 

Probably  tuberculous  infection  of  the  genital  ap- 
paratus is  secondary  to  a  focus  elsewhere.  Tuberculous 
infection  of  testes  usually  involves  the  seminal  ducts  and 
vesicles  by  extension  through  the  lymph  channels,  blood 


A  GENERAL  CONSIDERATION  13 

stream  or  vas  deferens.  This  focus  may  result  in  gen- 
eral tuberculosis  or  involve  the  urinary  bladder  and  kid- 
ney by  the  blood  stream  or  lymph  canals. 

Gonorrheal  vesiculitis  may  be  acute  or  chronic  and 
lead  to  gonorrheal  arthritis,  acute  or  chronic,  or  to  gon- 
orrheal bacteriemia,  and  ulcerative  endocarditis.  Infec- 
tion of  the  seminal  vesicles  may  be  due  to  streptococci 
and  staphylococci  and  cause  systemic  disease.  The  pros- 
tate gland  may  be  infected  with  gonococci,  streptococci, 
staphylococci,  tubercle  bacilli,  colon  bacilli  and  other 
less  important  bacteria.  When  infected  and  enlarged  it 
is  an  important  factor  in  infection  of  the  bladder,  ureters 
and  kidneys,  by  causing  urinary  obstruction  and  cystitis. 
Cystitis  may  be  due  to  pyogenic  bacteria,  tubercle  ba- 
cilli, bacillus  pyocyaneus,  typhoid  bacilli  and  other  bac- 
teria. The  colon  bacillus  is  a  very  common  inhabitant 
of  the  urinary  tract  and  usually  is  apparently  not  harm- 
ful. In  the  presence  of  bladder  stasis  and  in  other  types 
of  cystitis  (tuberculous,  streptococcus,  staphylococcus 
cystitis),  the  colon  bacteria  may  take  on  pathogenic 
qualities  as  a  mixed  infection.  Acute  and  chronic  cysti- 
tis may  be  the  source  of  infection  of  contiguous  tissues 
and  through  the  lymphatic  vessels  and  lymph  nodes  of 
the  base  of  the  bladder  and  in  the  walls  of  the  ureters, 
infection  of  the  pelvis  and  parenchyma  of  the  kidneys 
and  perirenal  tissues  may  occur  as  shown  by  S.  Sugi- 
mura  (4)  and  Carl  Franke  (5).  The  kidney  and  its 
pelvis,  however,  is  usually  infected  hematogenously  with 
pyogenic  bacteria,  typhoid,  colon  and  tubercle  bacilli  and 
other  microorganisms.  Indeed  cultures  of  the  urine, 
with  a  proper  technic,  will  yield  characteristic  bacteria, 


14  FOCAL  INFECTION 

during  the  incidence  of  many  infectious  general  and 
local  diseases,  as  shown  by  George  F.  Dick  and  Gladys 
R.  Dick  (6).  The  kidney  and  renal  pelvis  may  be 
the  site  of  focal  infection  which  may  cause  infection  of 
the  ureters  and  bladder  through  the  urine  contaminated 
with  tubercle,  colon,  typhoid  and  pyocyaneus  bacilli, 
pyogenic  cocci,  bacillus  proteus  and  with  other  bac- 
teria. 

Subcutaneous  abscesses  and  abscesses  about  the  nails 
are  occasionally  the  source  of  systemic  infection.  Fur- 
uncles and  carbuncles  are  well  known  sources  of  acute 
bacteriemia,  especially  in  patients  debilitated  by  ex- 
hausting diseases  of  which  diabetes  mellitus  is  an  ex- 
ample. 

SUSCEPTIBILITY  TO  SYSTEMIC  AND  LOCAL  DISEASES  FROM 
THE  FOCUS  OF  INFECTION 

The  high  percentage  of  incidence  of  localized  infec- 
tion, especially  about  the  head,  has  already  been  stated. 
The  greater  number  of  these  individuals  affected,  both 
young  and  old,  do  not  develop  acute  systemic  disease 
therefrom.  A  majority  of  children  suffer  from  chronic 
infection  of  the  tonsils  and  nasopharyngeal  lymphoid 
tissue  with  occasional  acute  exacerbations,  while  the  in- 
cidence of  acute  rheumatic  fever  and  endocarditis  is 
relatively  small  in  youth.  Nevertheless,  rheumatic 
fever  and  endocarditis  are  unquestionably  the  result  of 
focal  infection  of  the  mouth  and  throat. 

A  majority  of  civilized  mankind,  who  are  city  dwell- 
ers, carry  a  latent  tuberculous  focus,  usually  infected 
lymph  nodes  of  the  mediastinum,  mesentery  or  else- 


A  GENERAL  CONSIDERATION  15 

where  in  the  body.  A  comparatively  small  number  de- 
velop clinically  recognizable  tuberculosis. 

The  marked  prevalence  of  alveolar  abscess  is  not 
associated  with  the  frequent  incidence  of  acute  systemic 
infection.  Probably  the  frequent  relation  of  pyorrhea 
to  rheumatic  fever,  heart  disease,  nephritis  and  other 
acute  local  and  general  infections  has  not  been  given 
the  etiologic  importance  it  deserves.  Granting  this  fact 
one  must  still  recognize  the  comparatively  small  inci- 
dence of  acute  systemic  disease  arising  from  alveolar 
abscess. 

The  incidence  of  chronic  gonorrheal  infection  of  the 
prostate  gland,  seminal  vesicles,  vagina  and  fallopian 
tubes  is  very  large  as  compared  with  the  occurrence  of 
gonorrheal  arthritis,  tenovaginitis,  gonococcemia,  and 
ulcerative  endocarditis. 

The  escape  of  a  great  majority  of  persons  who  harbor 
foci  of  infection  from  manifest  clinical  systemic  disease, 
is  the  reason  given  by  many  thoughtful  physicians  for 
disbelief  in  the  etiologic  relation  of  foci  of  infection  to 
systemic  and  local  infection,  especially  of  the  chronic 
types. 

Based  upon  the  present  knowledge  obtained  by  clini- 
cal and  laboratory  research  and  experiments  upon  the 
lower  animals,  there  can  be  no  doubt  now  of  the  etio- 
logic relation  of  localized  infection  to  both  acute  and 
chronic  systemic  diseases.  Many  of  the  systemic  chronic 
processes  are  sequential  to  primary  acute  diseases,  etio- 
logically  related  to  focal  infection.  Other  chronic  sys- 
temic diseases  are  primarily  due  to  infection  derived 
from  focal  infection, 


16  FOCAL  INFECTION 

The  relatively  rare  incidence  of  systemic  disease  as 
compared  with  the  marked  prevalence  of  focal  infection 
may  be  answered,  partially,  at  any  rate,  by  well  known 
facts  concerning  immunity  both  natural  and  acquired. 

The  natural  defenses  of  the  body,  due  to  the  bacteri- 
cidal and  antitoxic  powers  of  the  tissues,  blood  plasma 
and  cells,  especially  the  phagocytes,  protect  the  major- 
ity of  us  from  the  acute  infectious  diseases.  All  individ- 
uals do  not  possess  an  equal  degree  of  natural  immunity ; 
some  more  readily  succumb  to  the  invading  infectious 
agents.  When  the  animal  body  is  invaded  with  patho- 
genic bacteria  the  natural  defenses  are  increased  by 
their  presence  in  the  tissues  and  blood.  The  processes 
are:  first,  the  phenomenon  of  positive  chemotaxis  with 
resulting  leukocytosis  and  the  accumulation  of  leu- 
kocytes in  the  areas  of  infection  of  the  tissues  by  the 
formation  of  local  exudates,  liquid  (purulent)  and  fi- 
brinoplastic,  which  may  serve  as  walls  of  protection 
against  further  direct  invasion;  second,  leukocytic 
phagocytosis  with  destruction  of  the  invading  bacteria; 
and  third,  the  formation  of  protective  antibodies  in  the 
blood  and  tissues. 

Similar  protective  processes  may  be  induced  in  the 
body  by  the  injection  of  non-lethal  amounts  of  living 
or  of  dead  pathogenic  bacteria  into  a  healthy  man  or 
animal. 

It  is  not  improbable  that  the  bacteria  of  a  focal  infec- 
tion may  excite  the  development  of  additional  defenses 
in  the  host  and  prevent  the  evolution  of  a  sequential 
systemic  disease. 

Bacteria  may  diminish  in  virulency  and  pathogenicity 


A  GENERAL  CONSIDERATION  17 

and  exist  as  harmless  parasites  of  the  skin,  mucous 
membranes  and  probably  also  as  foci  in  the  tissues 
(Kolle  and  Wassermann  (7)),  for  it  is  known  that 
the  reaction  of  the  tissues  is  influenced  by  the  virulence 
of  the  bacteria.  A  non-virulent  streptococcus  would  be 
disposed  of  by  the  tissues  with  but  little  local  or  gen- 
eral reaction. 

GREATER   SUSCEPTIBILITY   TO   SYSTEMIC   DISEASE    FROM    A 
FOCAL  INFECTION  UNDOUBTEDLY  OCCURS 

Immunity  both  natural  and  acquired  as  described  is 
not  absolute.  Pasteur  found  that  the  marked  immu- 
nity of  the  chicken  to  anthrax  could  be  overcome  by 
lowering  the  body  temperature  by  immersion  of  the 
fowl  in  cold  water.  It  is  known  that  physical  and  men- 
tal exhaustion,  starvation,  exposure  to  cold,  debility 
from  alcoholic  dissipation,  the  misuse  of  narcotic  drugs 
and  exhausting  general  disease  may  reduce  the  natural 
resistance. 

Innumerable  instances  of  the  incidence  of  the  sud- 
den onset  of  pneumonia,  rheumatic  fever,  tonsillitis, 
sinusitis,  nephritis,  septicemia  and  other  infectious  proc- 
esses have  been  recorded  after  exposure  to  extreme  cold. 
Undoubtedly  the  latent  pathogenic  bacteria  usually 
present  in  the  nose  and  throat  may  acquire  coincidently 
with  the  exposure  specific  pathogenicity,  and  are  able 
to  invade  the  host  because  of  the  lowered  resistance  and 
because  of  added  virulency.  The  acquisition  of  specific 
pathogenicity  and  tissue  affinity  by  the  members  of  the 
streptococcus-pneumococcus  group  will  be  fully  con- 
sidered. 


18  FOCAL  INFECTION 

Exhaustion  and  debility  from  physical  and  mental 
overwork,  starvation,  chronic  disease  and  other  condi- 
tions are  important  etiologic  factors  in  the  occurrence 
of  acute  and  chronic  systemic  disease  from  focal  in- 
fection. This  is  notably  true  of  the  chronic  infectious 
arthritis  and  myositis. 

Many  of  the  lesser  ills  of  the  body  in  the  form  of 
subjective  soreness  of  the  tissues,  joints,  muscles  and 
nerves  are  possibly  the  result  of  slight  infection  from  a 
focus  in  the  mouth  or  throat  or  some  other  region  of 
the  body,  especially  in  individuals  with  a  lessened  re- 
sistance. This  is  perhaps  a  vague  hypothesis,  but  in- 
stances of  the  disappearance  of  these  clinical  phenomena 
with  the  institution  of  individual  hygiene  and  removal 
of  an  existing  focus  of  infection  is  suggestive  of  the 
truth  of  the  statement. 

THE   DIAGNOSIS   OF   THE    FOCUS   OF   INFECTION 

Usually  a  focus  of  infection  is  disregarded  by  the 
patient  and  physician  unless  it  cause  local  discomfort. 
When  a  systemic  disease  occurs  which  present-day 
knowledge  associates  with  a  primary  infectious  focus, 
the  site  of  the  focus  must  be  located.  The  character 
of  the  systemic  disease  may  point  to  the  most  likely  lo- 
cation of  the  primary  portal  of  infection.  The  primary 
focus  of  acute  rheumatic  fever,  endocarditis,  chorea, 
myositis,  glomerulonephritis,  peptic  ulcer,  appendicitis 
and  chronic  deforming  arthritis,  as  examples,  is  usually 
located  in  the  head  and  usually  in  the  form  of  alveolar 
abscesses,  acute  or  chronic  tonsillitis  and  sinusitis.  One 
would  look  for  the  focus  of  gonorrheal  arthritis  in  the 


A  GENERAL  CONSIDERATION         19 

genito-urinary  tract.  The  failure  to  find  a  focus  in  the 
expected  situation  should  indicate  an  extension  of  the 
field  of  examination  until  the  primary  infection  shall 
have  been  found.  In  a  superficial  and  hasty  examina- 
tion the  site  of  the  focus  of  infection  may  escape  detec- 
tion or  the  focus  may  be  assumed  to  be  in  uninfected 
tissues  and  organs.  Every  patient  should  be  carefully 
interrogated  as  to  the  past  and  present  condition;  a 
general  examination  should  be  made,  including,  if  neces- 
sary, the  services  of  specialists  in  diseases  of  the  ear, 
nose  and  throat,  the  pelvic  organs  and  the  gastroin- 
testinal tract,  and  in  all  patients  with  evidence  of  pyor- 
rhea and  sinusitis  the  service  of  the  rontgenologist  is 
demanded.  Bacterial  cultures  made  from  the  surface 
of  the  gums  and  tonsils,  which  will  usually  yield  patho- 
logic types  of  bacteria,  are  not  an  index  of  focal  infec- 
tion located  in  the  dental  alveoli  or  tonsils.  In  alveolar 
abscess,  by  scraping  the  accumulated  "tartar"  and  exu- 
date from  the  exposed  neck  of  the  tooth  and  by  penetrat- 
ing as  deeply  as  possible  into  the  infected  alveolus,  one 
may  readily  obtain  material  for  microscopic  examination 
which  usually  yields  endameba  buccalis  and  bacteria. 
Cultures  of  the  feces  may  yield  strains  of  streptococci 
and  other  bacteria  not  usually  found  in  the  intestinal 
flora.  These  bacteria  may  not  be  specifically  pathogenic 
in  the  intestinal  habitat  and  if  free  in  the  intestinal  con- 
tents and  not  infecting  the  intestinal  structures  are 
quite  likely  not  to  be  harmful  to  the  host.  Bacterio- 
logical examination  including  cultures  should  always 
be  made  of  the  sputa,  urine,  uterine,  vaginal  and 
urethral  discharges  and  exudates  obtained  by  massage 


20  FOCAL  INFECTION 

of  the  prostate  gland  and  seminal  vesicles,  for  they 
often  yield  results  of  diagnostic  importance.  The  na- 
ture of  the  general  disease  and  its  relation  to  a  sup- 
posed focus  may  be  made  more  evident  by  the  coincident 
histologic  and  bacteriologic  studies,  both  miscroscopic 
and  cultural,  of  exudates  of  synovial  cavities,  and  of 
excised  lymph  nodes  proximal  to  the  infected  regions; 
bits  of  infected  muscles;  fibrous  nodes  on  tendons  and 
aponeuroses ;  the  blood,  and  also  of  the  exudate  of  the  fo- 
cus; and  by  the  inoculation  of  animals  with  strains  of 
the  dominant  pathogenic  bacteria  so  obtained,  while  the 
cultures  are  young.  The  discovery  of  the  similarity  of 
the  pathogenic  organisms  in  cultural  characteristics,  in 
the  focus  of  infection  and  in  the  infected  tissues,  and  the 
production  of  a  similar  infectious  process  in  the  inocu- 
lated animal  from  the  tissues  of  which  the  infectious  bac- 
teria are  afterwards  recovered,  constitute  reasonable 
proof  of  the  etiologic  relation  of  the  focus  of  infection  to 
the  existing  systemic  infection.  Many  successful  clinical 
and  laboratory  studies  of  this  kind  have  been  made  with 
patients  suffering  with  rheumatic  fever,  subacute  or 
chronic  infectious  endocarditis,  chronic  infectious  arth- 
ritis, appendicitis,  peptic  ulcer,  cholecystitis,  glomerulo- 
nephritis and  other  diseases. 

MODE  OF  DISSEMINATION  OF  BACTERIA  AND  TOXIC 
PRODUCTS  FROM  THE  FOCUS  OF  INFECTION 

Hematogenous 

Systemic  infection  and  intoxication  from  a  primary 
focus  is  usually  hematogenous.  The  bacteria  may  be 
compared  with  emboli  loosened  from  the  place  of  origin 


A  GENERAL  CONSIDERATION         21 

and  carried  in  the  blood  stream  to  the  smallest  and 
often  terminal  blood  vessels.  If  virulent  and  endowed 
with  specific  elective  pathogenic  affinity  for  the  tissues 
in  which  they  will  lodge,  and  if  in  sufficient  number,  the 
invading  bacteria  will  excite  characteristic  reactions  in 
the  infected  tissues  and  a  sequential  train  of  morbid 
anatomical  lesions.  The  evolution  of  the  anatomical 
lesions  and  the  clinical  phenomena  aroused  thereby  are 
dependent  on  the  type  and  virulence  of  the  bacteria, 
the  character  of  the  tissue  and  the  function  of  the  organ 
involved.  The  specific  tissue  reaction  consists  of  a  local 
inflammation  with  endothelial  proliferation  of  the  lining 
of  the  blood  vessel  with  or  without  thrombosis ;  blocking 
of  the  blood  vessels ;  hemorrhage  into  the  immediate  tis- 
sue ;  positive  chemotaxis  with  resulting  multiplication  of 
the  leukocytes  and  plasma  cells  in  the  infected  area,  or 
flbrinoplastic  exudate  with  local  connective  tissue  over- 
growth. 

Lymphogenous 

The  infectious  microorganisms  may  also  pass  from 
the  focus  to  other  tissues  through  the  lymph  channels 
and  lymph  nodes.  This  may  occur  from  the  primary  fo- 
cus coincidentally  with  hematogenous  systemic  infection. 
Primary  focal  infection  of  the  tonsils,  nasopharyngeal 
tissue,  the  accessory  sinuses  and  the  mastoid  cells  is  not 
infrequently  associated  with  secondary  infection  of  the 
lymphatic  vessels  and  lymph  nodes  of  the  neck,  some- 
times extending  to  the  mediastinal  lymph  nodes.  The 
lymph  nodes  which  drain  areas  of  tissues  which  have 
been  infected  hematogenously  from  a  primary  focus 
may  become  infected  and  enlarged  from  the  systemi- 


22  FOCAL  INFECTION 

cally  infected  areas  as  in  infected  joints,  cholecystitis, 
appendicitis  and  infection  about  the  pelvic  organs. 

The  tissue  reaction  which  occurs  in  infected  lymph 
nodes  varies  in  intensity  with  the  virulency  and  char- 
acter of  the  invading  bacteria.  Thus  a  varying  degree 
of  inflammation  results  in  proliferation  of  the  lymphoid 
cells  with  swelling  and  tenderness  of  the  nodes.  These 
secondary  foci  may  continue  as  active  depots  of  supply 
of  bacterial  infection  to  other  tissues.  If  the  invading 
bacteria  of  the  lymph  node  are  pyogenic  and  virulent, 
positive  chemotaxis  will  result  in  the  invasion  of  the 
infected  gland  with  leukocytes  and  a  circumscribed  ab- 
scess may  result.  Lymph  node  infection  with  necrotic 
changes  may  rupture  into  or  may  cause  infectious 
thrombophlebitis  in  a  contiguous  vessel  and  bacteriemia 
may  result.  In  other  instances  the  infection  in  the 
lymph  node  may  be  a  protection  by  holding  the  invad- 
ing organisms  in  a  tissue  environment  which  renders 
them  latent  and  for  the  time  harmless  to  the  patient. 

SYSTEMIC    INTOXICATION 

Systematic  intoxication  from  a  focus  of  infection  is 
characteristic  of  the  exotoxic  bacteria.  Diphtheria  and 
tetanus  are  two  examples  of  infectious  disease  in  which 
the  morbid  tissue  reactions  are  caused  by  soluble  toxins 
excreted  by  the  specific  microorganisms  in  a  focal  area. 

It  has  been  assumed  that  focal  infection  due  to  micro- 
organisms which  produce  endotoxins  may  cause  sys- 
temic disturbances  by  dissemination  of  toxic  substances 
from  the  focus.  It  is  suggested  that  the  toxic  material 
may  be  formed  by  biochemical  reactions  excited  by  the 


A  GENERAL  CONSIDERATION         23 

microorganisms  and  the  tissues  and  cellular  exudate  of 
the  focus;  also  that  autolysis  of  the  dead  microorgan- 
isms of  the  focus  sets  free  the  endotoxin.  Hence  it  is 
said  that  morbid  processes  of  a  degenerative  and  meta- 
bolic character  which  may  occur  in  many  organs  and  in 
varying  degrees  of  severity,  are  caused  by  toxins  and 
toxic  substances  elaborated  in  a  focus  of  infection. 

Semmelweis,  Klebs,  Virchow,  Pasteur,  Lister  and 
others  proved  long  ago  that  virulent  microorganisms 
are  the  cause  of  infectious  disease.  Modern  bacteriology 
and  clinical  research  are  adding  day  by  day  incontestable 
proof  that  bacterial  invasion  and  infection  of  tissue  is 
the  fundamental  cause  of  many  of  the  systemic  diseases, 
which  have  been  classed  as  toxic,  metabolic  or  nutri- 
tional. A  sequence  of  the  fundamental  and  primary 
infection  of  tissue  may  create  a  morbid  anatomy,  dis- 
turbed function,  malnutrition  and  in  consequence  sec- 
ondary metabolic  and  degenerative  changes.  The  endo- 
toxin of  the  invading  bacteria  is  set  free  in  the  blood  and 
tissues  and  is  a  factor  in  the  cellular  reaction  expressed 
in  general  infection  by  chill,  fever,  disturbed  functions 
and  altered  metabolism  and  in  local  infection  by  cellular 
reaction  and  symptoms  varying  with  the  character  of 
the  invading  bacteria,  the  anatomical  lesions  and  dis- 
turbance of  function  of  the  tissue  and  organ  involved. 

FOCAL  INFECTION  AND  ANAPHYLAXIS 

Focal  infection  may  be  the  cause  of  the  condition 
known  as  anaphylaxis.  The  bacterial  protein  of  the 
pathogenic  microorganism  of  the  focus  may  sensitize 
the  body  cells. 


24  FOCAL  INFECTION 

If  a  foreign  protein  gains  entrance  to  the  body  par- 
enterally,  via  the  blood  stream  or  the  lymphatics,  the 
animal  body  always  responds  to  the  parenteral  intro- 
duction of  the  foreign  protein  by  the  production  of 
specific  antibodies  to  that  foreign  albumen.  The  forma- 
tion of  the  specific  antibodies  requires  a  certain  period 
of  time.  After  this  interval  a  second  introduction  of 
the  same  protein,  again  by  a  parenteral  route,  results 
in  a  union  of  the  newly  formed  antibody  with  the  anti- 
gen (foreign  protein),  which  may  excite  physical  phe- 
nomena of  an  explosive  character.  These  phenom- 
ena, the  so-called  anaphylactic  shock,  differ  materially 
with  various  species  of  animals  and  with  man.  In  man 
the  typical  phenomena  may  consist  of  bronchial  spasm, 
urticaria,  vasodilatation  and  fall  of  blood  pressure,  eosin- 
ophilia,  physical  weakness  and  arthropathy.  In  some 
individuals,  urticaria  or  bronchial  asthma  may  be  the 
only  expression  of  anaphylaxis. 

Anaphylaxis  has  been  studied  as  serum  disease  by 
Rosenau  and  Anderson  (44),  Park  (47)  and  others. 
Von  Pirquet  (43),  Weil  (42),  Meltzer  (52)  and 
Vaughan  (45)  have  shown  the  relation  of  anaphylaxis 
to  the  symptom  expression  of  infectious  disease  and  to 
bronchial  asthma.  Theobald  Smith  (39),  Auer  and 
Lewis  (46),  Jobling,  Petersen  and  Eggstein  (53)  and 
many  others  have  reported  the  result  of  extensive  re- 
search upon  laboratory  animals  in  the  production  of 
immunity  and  of  anaphylaxis. 

The  relation  of  anaphylaxis  to  bronchial  asthma, 
many  dermatological  lesions,  gastro-intestinal  symp- 
toms,   cardiovascular    disturbance,    especially    arterial 


A  GENERAL  CONSIDERATION  25 

hypotension  and  other  morbid  conditions,  of  man,  lias 
not  received  the  attention  which  its  importance  de- 
mands. Definite  clinical  evidence  has  been  established 
of  the  etiologic  relation  of  confined  focal  infection  to 
anaphylaxis,  in  the  form  of  bronchial  asthma  and  other 
morbid  conditions.  The  subject  is  not  well  understood, 
but  is  so  important  that  it  demands  the  cooperative  re- 
search of  the  immunologist  and  clinician. 


LECTURE  II 

THE  STREPTOCOCCUS-PNEUMOCOCCUS  GROUP. 

TRANSMUTABILITY  OF  THE  MEMBERS  THEREOF. 
PATHOGENICITY  AND  SPECIFIC  TISSUE  AF- 
FINITY  OF   TRANSMUTATION   FORMS 

TRANSMUTATION  WITHIN  THE  MEMBERS  OF  THE  STREPTO- 
COCCUS-PNEUMOCOCCUS GROUP 

Recent  coordinate  research  in  clinical  medicine  and 
bacteriology,  fortified  by  animal  experimentation,  has 
made  more  evident  the  etiologic  relation  of  focal  infec- 
tion to  systemic  disease. 

The  main  and  fundamental  principles  which  have 
been  proved  are : 

1.  The  apparent  confirmation  of  the  transmutability 
of  the  members  of  the  streptococcus-pneumococcus 
group  in  variations  of  morphology,  cultural  character- 
istics, biological  reactions  and  also  of  general  and  spe- 
cial pathogenicity. 

2.  The  acquisition  of  pathogenic  elective  tissue  af- 
finity by  bacteria  in  foci  of  infection  in  culture  media 
and  serial  animal  passage. 

In  a  clinical  and  bacteriological  study  of  chronic  in- 
fectious endocarditis  Rosenow  (8)  and  Billings  (9) 
confirmed  the  report  of  Schottmuller  (10)  in  the  isola- 
tion from  the  blood  during  life  of  the  patient  of  a  pure 
culture  of  streptococcus  viridans.     Schottmuller    (10) 

26 


STREPTOCOCCUS-PNEUMOCOCCUS     27 

isolated  a  streptococcus  from  patients  with  chronic  in- 
fectious endocarditis,  which  grew  fine  colonies  on  blood 
agar  plates,  was  non-hemolyzing,  but  produced  a 
greenish  halo  around  the  colonies.  In  consequence  it 
was  named  streptococcus  viridans  and  because  of  its  low 
pathogenicity  for  animals  it  was  also  called  strepto- 
coccus mitior.  The  streptococcus  viridans,  isolated  from 
the  blood  of  our  eleven  patients,  was  cultivated  in  vari- 
ous media  and  animals  were  inoculated  with  successive 
strains.  The  behavior  of  the  strains  obtained  from  all 
patients  was  the  same.  The  end  result  was  a  pneumo- 
coccus  of  specific  pathogenicity  for  animals  in  the  pro- 
duction of  pneumococcemia  and  pneumonia. 

In  consequence  of  these  results  the  bacteriological 
diagnosis  of  our  series  of  observed  patients  was  chronic 
pneumococcus  endocarditis.  Rosenow  soon  recognized 
the  fact  that  the  bacteria  studied  were  typical  pneumo- 
cocci  and  that  transmutation  of  the  original  pure  cul- 
ture of  streptococcus  viridans  had  occurred  in  form, 
culture  characteristics  and  in  general  and  special  patho- 
genic virulence  for  animals. 

Since  that  time  Rosenow  (8)  has  apparently  con- 
firmed the  transmutability  of  the  members  of  the  strep- 
tococcus group  and  that  the  property  of  trans- 
mutation is  reversible  within  the  members  of  this  fam- 
ily. He  says:  "From  this  study  the  apparent  po- 
sition of  the  various  members  of  the  streptococcus 
group  may  be  illustrated  by  the  position  of  the  fingers 
in  a  partially  flexed  hand,  in  which  the  hemolytic 
streptococcus  occupies  the  position  of  the  little  finger, 
the  pneumococcus  the  place  of  the  index  finger  (the  op- 


28 


FOCAL  INFECTION 


posite  extreme),  streptococcus  viridans  (representing 
the  group  of  more  or  less  saprophytic,  non-hemolyzing 
streptococci)  the  middle  finger,  the  streptococci  from 
rheumatism  the  ring  finger,  and  streptococcus  mucosus, 
having  some  of  the  properties  of  both  pneumococci  and 
streptococci,  the  thumb.  In  this  grouping  there  is  in 
general  an  increase  in  parasitism  and  virulence  as  we 


Fig.  1. — Strain  595  as  a  Hemolytic  Streptococcus  Isolated  from  a  Case 
of  Scarlet  Fever.  Smear  from  24  hour  culture  in  ascites-dextrose- 
broth.     Gram  stain. 

approach  the  thumb  (streptococcus  mucosus)."  Rose- 
now  has  arrived  at  this  conclusion  by  working  with 
strains  of  streptococci  and  pneumococci  obtained  from 
various  sources:  Strains  of  hemolytic  streptococci  iso- 
lated from  patients  suffering  from  erysipelas,  puerperal 
sepsis,  scarlatina,  acute  tonsillitis  and  acute  polyar- 
thritis; from  cow's  milk  and  other  sources;  strains  of 
streptococcus  viridans  isolated  from  tonsils,  alveolar 
abscesses,  the  blood,  from  other  tissues  and  cow's  milk; 
streptococcus  mucosus  from  sputa,   tonsils   and   else- 


STREPTOCOCCUS-PNEUMOCOCCUS     29 


Fig.  2. — Strain  595  as  Streptococcus  Viridans.     Smear  from  24  hour  cul- 
ture in  ascites-dextrose-broth.     Gram  stain. 

where  and  pneumococci  isolated  from  sputa,  the  blood 
during  life  and  post  mortem,  the  exudate  of  empyema, 
from  hepatized  lung  and  also  Cole's  (11)  strains  I  and 


Fig.   3. — Strain   595   as   a   Pneumococcus.     Smear    from   24   hour   culture 
in  ascites-dextrose-broth.     Capsule  stain. 


30 


FOCAL  INFECTION 


II.  These  have  been  successfully  made  to  assume  the 
varying  types  as  to  form,  cultural  characteristics,  bio- 
logic reactions  and  special  and  general  pathogenic  viru- 
lence of  the  group. 

The  technic  which  Rosenow  pursues  consists  of  the 
use  of  the  ordinary  solid  and  liquid  culture  media  in 
which  the  oxygen  content  is  increased  and  decreased, 


Fig.  4. — Strain  of  Streptococcus  from  Rheumatism  Which  Produced 
Slight  Hemolysis  on  Blood  Agar  and  Myositis  in  Animals.  Smear 
from  blood  agar  slant.     Capsule  stain. 

the  use  of  hypotonic  and  hypertonic  media,  cultures 
made  in  symbiosis  with  bacillus  subtilis  as  the  occasion 
may  indicate  and  of  serial  animal  inoculation.  Haessli 
(12)  produced  transmutation  of  a  non-color-forming 
strain  of  streptococcus  f  ecalis,  by  passing  it  several  times 
through  horse  serum,  when  it  finally  became  strongly 
hemolytic  and  had  acquired  all  the  pathogenic  charac- 
teristics of  streptococcus  erysipelas.  By  the  same 
method   streptococcus   viridans   first   lost   its   greenish 


Fig.  5. — The  Same  Strain  as  in  Fig.  4  After  It  Was  Transformed  Into 
a  Pneumococcus.     Smear  from  blood  agar  slant.     Capsule  stain. 


Fig.  6. — Highly  Virulent  Pneumococcus.  Type  1.  Originally  Isolated 
by  Neufeld.  Smear  from  surface  and  water  of  condensation  of  blood 
agar  slant.     Capsule  stain. 


31 


32 


FOCAL  INFECTION 


color  producing  quality,  finally  became  hemolytic  and 
a  strain  of  streptococcus  mucosus  became  hemolytic. 
Haessli  finally  states  that  his  experiments  confirm  the 
clinical  differentiation  of  streptococci  as  demonstrated 
by  Schottmuller.  Schottmuller  (10)  probably  recog- 
nized the  transmutability  of  members  of  the  streptococ- 
cus group  pathogenic  for  man  which  he  classified  as 


Fig.  7. — The  Same  Strain  as  in  Fig.  6  After  Transformation  Into  Hemo- 
lytic Streptococcus.  Smear  from  surface  and  water  of  condensation 
of  blood  agar  slant.     Capsule  stain.  • 

streptococcus  longus  (hemolysans) ,  streptococcus  mitior 
(viridans)  and  streptococcus  mucosus.  Schottmuller 
(10)  also  described  strains  of  streptococcus  mucosus, 
which  possessed  all  the  characteristics  of  strains  first  iso- 
lated from  patients  with  parametritis  in  1896,  obtained 
in  pure  culture  from  the  blood  and  hepatized  lung  of  five 
patients  with  clinical  lobar  pneumonia.  The  strains  de- 
scribed occurred  as  diplococci  with  capsule  in  chains  of 
ten  to  fourteen  pairs.  Evidently  he  did  not  recognize 
the  pneumococcus  as  a  member  of  the  group  and  espe- 


STREPTOCOCCUS-PNEUMOCOCCUS     33 

cially  its  close  relation  to  the  streptococcus  mucosus. 
Transmutation  within  the  members  of  other  groups  of 
pathogenic  bacteria  probably  occurs.  The  members  of 
the  colon-typhoid  group  shade  into  one  another  in 
form,  motility,  cultural  characteristics  and  in  degrees  of 
pathogenicity  from  nil  to  exalted  virulence. 

Virulence  and  Elective  Pathogenic  Tissue  Affinity 

The  varying  virulence  of  facultative  pathogenic  bac- 
teria has  been  long  recognized.  Environment  seems  to 
play  an  important  role.  This  seems  especially  true  of 
living  tissue  environment.  Not  only  may  there  be  a 
variation  in  general  virulence,  but  apparently  a  special 
pathogenic  virulence  for  certain  tissues  may  be  acquired. 
In  this  connection  we  may  note  the  recent  epidemics  of 
septic  tonsillitis,  frequently  associated  with  fatal  bac- 
teriemia,  due  to  milk  infected  with  streptococci  from 
human  carriers.  The  acquirement  of  a  selective  specific 
tissue  affinity  by  a  strain  of  streptococci  has  been  noted 
by  Forssner  (13).  By  culture  in  kidney  and  kidney 
extract  the  ordinary  streptococcus  pyogenes  (hemoly- 
sans),  which  had  no  pathogenic  elective  affinity  for  the 
kidney,  was  converted  into  a  strain,  which  injected  in- 
travenously into  animals  constantly  produced  outspoken 
anatomical  lesions  of  the  kidney.  This  Forssner  be- 
lieves is  positive  proof  that  the  bacteria  of  a  local  in- 
fection may  attain  a  specific  pathogenic  and  elective 
tissue  affinity. 

By  making  continued  cultures  in  bouillon,  for  a  long 
time  these  specific  kidney  strains  assumed  a  general 
virulence.    Again  grown  on  kidney  and  kidney  extract, 


34  FOCAL  INFECTION 

the  specific  kidney  pathogenicity  was  regained  and 
maintained  through  numberless  generations.  This  spe- 
cific kidney  pathogenicity  was  lost  after  a  few  genera- 
tions in  continued  bouillon  cultures.  The  general  viru- 
lence was  also  finally  lost. 

Poynton  and  Paine  (14)  in  a  discussion  of  the  re- 
lation of  malignant  to  rheumatic  endocarditis  state  that 
the  diplococcus  isolated  from  patients  with  acute  rheu- 
matism caused  acute  non-suppurative  arthritis  and  sim- 
ple rheumatic  endocarditis  in  rabbits.  In  culture  after 
a  few  months  the  same  strain  of  diplococci  caused  ma- 
lignant endocarditis  in  the  inoculated  animal.  They 
could  not  recover  the  diplococcus  from  the  nodular  vege- 
tations in  rheumatic  endocarditis,  but  succeeded  in  ob- 
taining pure  cultures  of  a  smaller  diplococcus  from  the 
large  vegetations  and  contained  thrombi  of  malignant 
endocarditis.  They  concluded  that  the  diplococcus 
rheumaticus  was  capable  of  producing  not  only  arthritis 
and  rheumatic  endocarditis  but  also  malignant  endo- 
carditis. Rationally  we  may  interpret  their  observa- 
tions and  results  as  a  transmutation  of  the  diplococcus 
rheumaticus  in  virulency  and  in  specific  pathogenicity. 
Our  clinical  observations  and  Rosenow's  experiments 
seem  to  show  that  the  members  of  the  streptococcus- 
pneumococcus  group  may  acquire  specific  pathogenic 
elective  affinity  for  certain  tissues  in  the  primary  focus 
and  also  in  the  tissues. 

Clinical  examples  have  been  observed  of  acute  ap- 
pendicitis; cholecystitis;  acute  gastric  and  duodenal 
ulcer;  acute  and  subacute  glomerulonephritis;  rheumat- 
ic fever;  erythema  nodosum;  herpes  zoster;  malignant 


STREPTOCOCCUS-PNEUMOCOCCUS     35 

endocarditis ;  simple  endocarditis ;  myocarditis  and  other 
acute  and  chronic  systemic  diseases,  associated  with  co- 
incident focal  infection  of  the  tonsils,  accessory  sinuses, 
dental  alveoli,  the  skin  and  its  appendages,  the  fallopian 
tubes,  the  prostate  and  seminal  vesicles  and  other  foci. 
Dominant  pathogenic  bacteria  have  been  isolated  from 
tissues  and  exudates  of  patients  at  surgical  operation; 
by  blood  culture;  from  the  urine;  from  joint  exudates 
and  pieces  of  tissue  (muscular,  lymphoid,  joint  capsules 
and  fibrous  nodes),  removed  with  the  consent  and  often 
at  the  request  of  patients.  These  cultures  have  been 
intravenously  injected  into  laboratory  animals  and  at 
the  same  time  cultures  of  bacteria  isolated  from  the 
primary  foci  of  the  patients  have  been  likewise  used 
to  inoculate  other  animals. 

The  evidences  of  the  specific  elective  tissue  affinity  of 
the  pathogenic  streptococci  from  the  various  tissues  and 
likewise  of  the  primary  foci  is  very  marked.  This  is 
significantly  expressed  in  the  following  table  prepared 
by  Rosenow  (8)  from  an  enormous  number  of  animal 
experiments. 

The  principles  of  localized  infection  in  man  and  ani- 
mals are  so  important  that  the  technic  of  the  experi- 
ments and  the  interpretation  of  the  table  by  Rosenow 
are  quoted  very  fully  here. 

Technic 

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four  hours  at  37°  C.  in  tall  columns  of  ascites  (10  per  cent.) 
dextrose  (0.2  per  cent.)  broth  (0.6+  to  0.8-}-)  to  which 
sterile  tissue  (guinea-pig  kidney  or  heart  muscle)  was  often 
added;  the  sterility  of  the  ascites  fluid  and  broth  containing 


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STREPTOCOCCUS-PNEUMOCOCCUS     37 

the  tissue  was  always  proved  beforehand.  After  incubation 
smears  were  made,  the  cultures  were  centrifuged  in  the  con- 
tainers in  which  they  were  cultivated,1  the  supernatant  fluid 
was  decanted  and  the  sediment  suspended  in  sodium  chlorid 
solution  so  that  1  c.c.  of  the  suspension  contained  the  growth 
from  15  c.c.  of  broth.  The  doses  for  rabbits  (ear  vein)  were 
usually  from  0.5  to  3  c.c,  and  for  dogs  (leg  vein)  from  1  to 
5  c.c.  of  this  suspension.  The  injections  were  made  quite 
rapidly  through  a  rather  fine  needle  (22  gauge),  usually  within 
an  hour  after  the  suspension  was  made.  Blood  agar  plate  cul- 
tures were  made  at  the  time  the  suspensions  were  injected  to 
study  the  character  of  the  organisms,  to  test  their  viability  and 
to  save  them  for  further  study.  This  is  an  important  precau- 
tion because  negative  results  have  at  times  proved  to  be  due  to 
early  death  of  the  recently  isolated  organisms  in  the  broth 
cultures.  In  the  accompanying  table,  "when  isolated"  indi- 
cates the  first  or  second  and,  occasionally,  the  third  or  fourth 
cultures,  or  the  first  culture  after  one  animal  passage.  "Later" 
indicates  that  the  strains  were  cultivated  for  a  week  or  longer. 
"After  animal  passage"  indicates  usually  from  the  second  to 
the  sixth  animal  passage. 

The  strains  tested  from  appendicitis,  ulcer  of  the  stomach, 
cholecystitis,  rheumatic  fever,  erythema  nodosum,  myositis  and 
endocarditis  include  strains  isolated  from  the  characteristic 
lesions  as  well  as  from  the  apparent  atrium  of  infection.  Those 
from  herpes  zoster  were  from  the  tonsils  and  spinal  fluid,  and 
those  from  epidemic  parotitis  were  obtained  by  catheterizing 
Steno's  duct  and  from  the  tonsils.  The  strains  from  miscel- 
laneous sources  were  usually  from  tonsils  approaching  the 
normal  condition ;  and  the  laboratory  strains  were  streptococci 
or  pneumococci  cultivated  on  artificial  mediums  for  a  long  time 
and  had  lost  all  apparent  virulence.  The  figures  in  the  lowest 
line  of  the  table  represent  the  average  percentage  incidence 

1  The  common  8-ounce  nursing  bottle  is  used  both  as  a  culture 
flask  and  centrifugal  tube,  and  serves  the  purpose  admirably. 


38  FOCAL  INFECTION 

of  lesions  in  individual  organs  following  injection  of  various 
strains  of  streptococci  except  those  from  the  specific  disease. 
Thus  the  first  figure  indicates  that  5  per  cent,  of  the  animals, 
injected  with  the  various  strains  except  those  from  appendi- 
citis, showed  lesions  in  the  appendix. 

Care  was  exercised  to  obtain  growths  from  the  depths  of  the 
supposed  primary  focus  with  as  little  contamination  from  the 
surface  as  possible,  the  cultures  being  made  from  the  material 
expressed  from  the  tonsils  or  from  emulsion  of  extirpated 
tonsils  after  thorough  washing  in  sodium  chlorid  solution.  The 
material  from  the  depths  of  pyorrheal  pockets  was  obtained 
by  means  of  a'  pipet. 

For  the  study  of  pathogenicity  of  the  cultures,  dogs  and  rab- 
bits were  chiefly  used,  being  killed  with  chloroform  at  the  de- 
sired time,  usually  in  from  twenty-four  to  forty-eight  hours. 
Post  mortem  examinations  were  always  made  as  soon  after 
death  as  possible.  A  thorough  inspection  in  a  bright  light  with 
the  unaided  eye  or  with  the  aid  of  a  hand  lens  was  made  for 
focal  lesions.  The  exact  character  of  the  lesions  and  the  pres- 
ence of  the  streptococci  in  each  of  the  various  diseases  have 
been  determined  by  microscopic  study  of  sections.  Cloudy 
swelling  is  not  included  in  the  results  given  in  the  table.  Hemor- 
rhage, localized  necrosis,  exudation  and  infiltration  were  the 
usual  lesions.  Thus,  in  case  of  the  joints,  hemorrhage  about  the 
joint  or  turbidity  of  fluid,  as  determined  with  a  pipet,  or  both, 
were  considered  as  evidence  of  arthritis.  Hemorrhages  in  the 
pericardium  and  turbidity  of  pericardial  fluid,  due  to  leu- 
kocytes, were  considered  as  evidence  of  pericarditis.  The  post 
mortem  study  of  animals  often  symptomless  is  essential  to  ob- 
tain accurate  knowledge  of  the  pathogenicity  of  a  culture,  and 
must  supplant  the  older  method  of  merely  finding  out  whether 
a  culture  produces  death  or  not,  a  method  still  too  much  in 
vogue.  The  table  includes  data  only  from  those  animals  in 
which  the  post  mortem  was  comprehensive,  and  does  not  in- 
clude some  of  the  earlier  experiments,  especially  on  endocardi- 


STREPTOCOCCUS-PNEUMOCOCCUS     39 

tis.  Increase  in  mortality  rate,  earlier  death  and  greater  de- 
gree and  distribution  of  lesions  following  standard  dosage  were 
considered  as  proof  of  high  virulence.  Changes  in  the  spleen 
and  liver  were  so  rare  following  injection  of  the  strains  as 
isolated,  except  those  from  cholecystitis,  that  they  are  not 
included  in  the  table.  Acute  splenitis  and  such  changes  in  the 
liver  as  focal  necrosis,  parenchymatous  and  bile  duct  hemor- 
rhages and  acute  degeneration  with  marked  acidity  occurred, 
however,  after  the  strains  had  acquired  greater  virulence  from 
animal  passage.  In  the  earlier  experiments  not  sufficient  at- 
tention was  paid  to  the  occurrence  of  lesions  in  the  thyroid, 
thymus,  suprarenals  and  lymphatic  glands.  Later  a  closer 
search  for  lesions  in  these  structures  was  made,  especially  after 
it  was  found  that  lesions  in  the  thyroid  followed  intravenous 
injection  of  bacteria  isolated  from  goiter.  It  must  be  said,  too, 
that  strains  of  streptococci  from  rheumatic  fever,  myositis  and 
cholecystitis  produce  hemorrhages  in  the  thyroid  quite  com- 
monly, while  those  from  other  sources  rarely  produce  them. 

Results 

A  study  of  the  table  shows  that  streptococci  from  the  various 
diseases  often  have  a  most  striking  affinity  or  tropism  for  the 
organs  or  tissues  from  which  they  are  isolated.  Thus,  fourteen 
strains  from  appendicitis  produced  lesions  in  the  appendix  in 
68  per  cent,  of  the  sixty-eight  rabbits  injected,  which  is  in 
marked  contrast  to  an  average  of  only  5  per  cent,  (given  in 
lowest  line  of  table)  of  lesions  in  the  appendix  in  the  animals 
injected  with  the  strains  as  isolated  from  sources  other  than 
appendicitis.  Eighteen  strains  from  ulcer  of  the  stomach  or 
duodenum  produced  hemorrhages  in  60  per  cent,  and  ulcer  of 
the  stomach  or  duodenum  in  60  per  cent.,  a  combined  total  of 
74  per  cent,  of  the  103  animals  injected,  in  contrast  to  an  aver- 
age of  20  per  cent,  hemorrhages  and  9  per  cent,  ulcer  following 
injection  of  other  strains.  Twelve  strains  from  cholecystitis 
produced  lesions  in  the  gall-bladder  in  80  per  cent,  of  the  forty- 


40  FOCAL  INFECTION 

one  animals  injected,  in  contrast  to  an  average  incidence  of  le- 
sions here  of  only  11  per  cent,  with  the  other  strains.  Twenty- 
four  strains  from  rheumatic  fever  produced  arthritis  in  66  per 
cent.,  endocarditis  in  46  per  cent.,  pericarditis  in  27  per  cent., 
and  myocarditis  in  44  per  cent,  of  the  seventy-one  animals  in- 
jected, in  contrast  to  an  average  of  arthritis  in  27  per  cent., 
endocardial  lesions  in  14  per  cent.,  pericarditis  in  2  per  cent, 
and  myocarditis  in  10  per  cent,  of  the  animals  injected  with 
strains  from  sources  other  than  rheumatic  fever.  Six  strains 
from  erythema  nodosum  produced  lesions  of  the  skin  in  90  per 
cent,  of  twenty  animals  injected,  in  contrast  to  an  average  of 
2  per  cent,  in  the  animals  injected  with  the  strains  from  sources 
other  than  erythema  nodosum  and  herpes  zoster.  Eleven  strains 
from  herpes  zoster  produced  herpetiform  lesions  of  the  skin, 
lips,  tongue  or  conjunctivae  in  77  per  cent,  of  the  sixty-one 
animals  injected,  in  contrast  to  the  average  of  only  1  per 
cent,  of  what  seemed  to  be  herpes  of  the  skin  with  the  other 
strains.  Nine  strains  of  streptococcal  organisms  from  epidemic 
parotitis  produced  lesions  in  one  or  both  parotid  glands  in  73 
per  cent,  of  the  nineteen  animals  injected  intravenously,  in  con- 
trast to  no  instance  of  lesions  here  with  the  other  strains.  Three 
strains  from  cases  of  true  myositis  produced  myositis  in  75  per 
cent,  and  myocarditis  (chiefly  of  the  right  ventricle)  in  35  per 
cent,  of  the  forty  animals  injected,  in  contrast  to  an  average 
of  myositis  of  12  per  cent,  and  myocarditis  of  10  per  cent, 
following  injection  of  strains  from  sources  other  than  myositis 
or  rheumatic  fever  and  eight  strains  of  streptococcus  viridans 
from  chronic  septic  endocarditis  produced  lesions  in  the  endo- 
cardium in  84  per  cent,  of  the  forty- four  animals  injected,  in 
contrast  to  an  average  of  15  per  cent,  with  the  strains  other 
than  those  from  endocarditis.  The  results  following  injection 
of  the  miscellaneous  strains  (usually  the  first  culture  from  ton- 
sils) and  the  laboratory  strains  serve  as  a  basis  of  comparison 
with  those  following  injection  of  the  strains  from  the  various 
diseases,  and  correspond  roughly  with  the  total  average  inci- 


STREPTOCOCCUS-PNEUMOCOCCUS     41 

dence-  of  lesions  in  the  various  organs  as  given  in  the  lowest  line 
of  the  table. 

While  the  incidence  of  lesions  in  the  organs  following  injec- 
tion of  the  strains  isolated  from  such  organs  is  high,  as  shown 
by  these  figures,  the  appearances  at  the  necropsy  are  even  more 
significant.  In  many  instances  in  which  the  animals  survive  the 
injection  for  some  time,  no  other  focal  lesions  could  be  found 
except  those  in  the  organ  in  question ;  and  when  the  animal 
died  early,  these  lesions  were  the  marked  feature  and  the  asso- 
ciated ones  were  relatively  insignificant.  Frequently  the  injec- 
tion of  a  very  small  dose  was  sufficient  to  prove  the  elective 
localization.  This  elective  property  was  shown  not  only  by 
the  cultures  from  tissues  and  foci  but  also  by  the  bacteria  con- 
tained in  the  foci,  directly  injected  in  other  animals. 

In  many  cases  of  both  acute  and  chronic  diseases  the  ap- 
parent atrium  of  infection  was  found  to  harbor  streptococci 
having  elective  affinity ;  in  the  former  usually  only  at  the  time 
of  the  attack,  in  the  latter  in  some  instances  for  months.  The 
elective  affinity,  however,  was  less  marked  in  the  strains  isolated 
from  the  supposed  focus  than  in  the  strains  isolated  from  the 
lesions  in  the  various  organs.  The  rather  wide  range  of  lesions, 
as  indicated  in  the  table,  following  the  injection  of  the  strains 
from  herpes  zoster  and  parotitis  is  due  to  the  fact  that  often 
primary  mixed  cultures  from  tonsils  and  pyorrheal  pockets 
were  injected. 

Attempts  to  find  a  method  which  would  preserve  the  original 
tropic  property,  while  only  partially  successful,  have  shown 
that  it  may  be  preserved  for  some  weeks  in  the  deeper  colonies 
of  the  original  shake  cultures  and  for  as  long  as  seven  months  by 
keeping  the  suspensions  containing  sterile  tissue  in  the  ice  chest, 
thus  maintaining  the  bacteria  in  a  condition  of  latent  life. 

The  localization  of  the  strains  from  appendicitis,  ulcer  of 
the  stomach  and  cholecystitis  as  isolated,  after  cultivation  and 
after  animal  passage,  is  of  particular  interest.  It  should  be 
stated  here,  however,  that  these  strains  resemble  one  another 


42  FOCAL  INFECTION 

very  closely  indeed  in  cultural  and  other  respects.  Those  from 
appendicitis  are  the  least  virulent,  those  from  ulcer  occupy 
a  middle  position  and  those  from  cholecystitis  are  the  most 
virulent.  The  virulence  seems  to  be  one  of  the  factors  that 
determine  their  place  of  survival  after  intravenous  injection. 
Now  if  the  localization  is  dependent  to  a  certain  extent  on 
virulence,  then  the  occurrence  of  ulcer  and  cholecystitis  should 
become  greater  as  the  strains  from  the  appendix  are  passed 
through  animals,  and  appendicitis  should  occur  oftener  after 
the  strains  from  ulcer  and  cholecystitis  lose  virulence  from 
cultivation  on  artificial  mediums.  This  is  found  actually  to 
be  the  case  (see  figures  in  table).  In  this  connection  other 
facts  should  be  mentioned.  None  of  the  strains  from  appen- 
dicitis produced  pancreatitis.  The  strains  from  ulcer  and 
cholecystitis  as  isolated  (mostly  those  from  acute  cases)  pro- 
duced pancreatitis  in  3  per  cent,  and  5  per  cent.,  respectively, 
of  the  animals  injected.  After  animal  passage,  pancreatitis 
occurred  in  15  and  19  per  cent,  respectively,  while  after  culti- 
vation on  artificial  mediums  pancreatitis  in  no  case  was  ob- 
tained. 

Lesions  in  the  intestines,  exclusive  of  the  duodenum,  were 
more  common  with  the  strains  from  cholecystitis  and  rheuma- 
tism than  with  those  from  appendicitis,  and  all  the  strains  pro- 
duced intestinal  lesions  (chiefly  of  the  mucous  membrane  and 
lymphoid  structures)  quite  commonly  after  they  had  been 
passed  through  animals,  whereas,  after  cultivation  for  a  time, 
no  noteworthy  lesions  were  found  in  the  intestinal  tract. 

The  streptococci  studied  from  parotitis  resemble  the  organ- 
ism described  by  Herb 1  and,  like  hers,  produced  the  char- 
acteristic picture  of  mumps  in  dogs  when  injected  into  Steno's 
duct.  Intravenous  injection  of  these  organisms  produced 
marked  edema  and  hemorrhage  in  and  surrounding  the  parotid. 
The  affinity  was  so  great  that  the  streptococci  were  found  in 

1  Herb,  Isabella  C. :  Experimental  Parotitis,  Arch,  Int.  Med., 
September,  1909,  p.  201, 


STREPTOCOCCUS-PNEUMOCOCCUS     43 

pure  culture  in  the  enlarged  parotid  in  three  of  five  full-time 
puppies  removed  from  the  uterus  of  a  dog  which  was  chloro- 
formed during  a  marked  parotitis  following  injection  into 
Steno's  duct.  Antigens  prepared  from  a  number  of  these  strains 
were  found  to  bind  specifically  complement  in  serum  from  paro- 
titis (Howell). 

Lesions  in  the  skeletal  muscles  occurred  in  75  per  cent,  of 
the  animals  injected.  The  number  of  lesions  in  the  muscles  and 
myocardium  in  the  animals  injected  with  strains  from  myositis 
was  often  in  proportion  to  the  quantity  injected,  and  occurred 
mostly  in  the  tendinous  portion  and  in  the  right  ventricle. 

Lesions  in  the  kidney  were  especially  common  after  injec- 
tions of  streptococci  from  rheumatic  fever  (39  per  cent.)  and 
from  endocarditis  (20  per  cent.).  These  occurred  chiefly  in  the 
medullary  portion  in  the  former  and  in  the  glomeruli  in  the 
latter. 

Lesions  in  the  lung,  consisting  usually  of  hemorrhages  and 
edema,  were  rare  following  injection  of  the  strains  when  iso- 
lated and  after  they  were  cultivated  on  artificial  mediums  but, 
just  as  was  found  previously,  they  occurred  oftener  after  the 
virulence  was  increased  by  animal  passage. 

That  the  streptococci  are  the  underlying  cause  of  the  dis- 
eases from  the  lesions  of  which  they  were  isolated  is  indicated 
further  by  the  fact  that  they  have  elective  affinity  for  the 
corresponding  structures  in  animals.  Moreover,  the  fact  that 
the  same  streptococcus  may  be  made  to  localize  in  different  or- 
gans is  in  consonance  with  the  knowledge  that  streptococci  may 
cause  diseases  with  different  symptomatology.  The  possibility, 
however,  that  they  are  secondary  invaders  to  some  ultramicro- 
scopic,  filterable  organism  has  to  be  considered.  Filtrates  of 
the  streptococcal  cultures  from  various  diseases  were  injected 
in  the  organs  from  which  the  strains  were  isolated ;  the  lesions, 
however,  were  not  due  to  living  organisms  because  the  broth 
which  was  inoculated  and  incubated  with  the  tissues  failed  to 
produce  any  lesions.     The  results,  while  inconclusive,  may  be 


44  FOCAL  INFECTION 

said  to  indicate  that  streptococci  produce  substances  which 
cause  injury  specifically  in  the  tissues  from  which  the  strains 
are  isolated. 

********* 

Although  the  circulation  is  an  important  factor  in  determin- 
ing localization,  the  tissues  themselves  play  an  even  more  im- 
portant role.  The  question  whether  the  lesions  in  the  organ 
for  which  a  particular  strain  appears  to  have  elective  affinity 
are  due  to  the  lodgment  of  a  larger  number  of  bacteria  here 
than  in  the  other  organs,  or  whether  the  bacteria  lodged  in 
equal  numbers  in  the  various  organs  but  survive  only  in  the 
one  showing  lesions,  is  now  under  study.  The  evidence  already 
obtained,  however,  points  strongly  to  the  former  mechanism. 
It  appears  that  the  cells  of  the  tissues  for  which  a  given  strain 
shows  elective  affinity  take  the  bacteria  out  of  the  circula- 
tion as  if  by  a  magnet- — adsorption. 

This  remarkable  tropic  condition  tends  to  disappear  quite 
promptly  both  on  cultivating  the  streptococci  on  artificial  me- 
diums and  on  passing  them  successively  through  animals,  and 
this  may  occur  without  demonstrable  changes  in  morphology, 
grouping  or  character  of  chain  formation.  I  have  previously 
shown  that  the  ability  of  streptococcus  viridans  and  staphylo- 
cocci to  produce  lesions  in  the  endocardium  is  due  partly  to 
physical  clumping.  A  careful  study  of  smears  of  the  suspensions 
injected  in  these  experiments  revealed  no  constant  relation 
between  localization  and  clumping  or  size  of  the  bacteria. 

Individual  variations  in  resistance  to  infection  were  found 
in  the  injected  animals.  The  effects  of  these  conditions  in  the 
host  as  determining  factors  in  localization  are  important ;  they 
are  probably  expressions  of  differences  in  metabolism,  oxidation 
rates,  etc.,  which  influence  the  soil  for  bacteria.  The  tendency 
of  virulent  bacteria,  temporarily  or  permanently,  to  render  this 
soil  less  favorable  for  their  growth  is  well  established.  There 
is  some  evidence,  on  the  other  hand,  which  goes  to  show  that 
certain  bacteria  of  very  low  virulence   (commonly   found  in 


STREPTOCOCCUS-PNEUMOCOCCUS     45 

chronic  foci  of  infection)  tend  actually  to  make  this  soil  more 
favorable.  But  it  must  be  considered  that  differences  in  the 
host  may  afford  the  peculiar  type  of  reaction,  or  that  the 
individual  harbors  a  particular  form  of  focus  of  infection  which 
is  favorable  for  bacteria  to  acquire  elective  properties.  The 
following  facts  support  the  latter  view:  (1)  the  common  occur- 
rence of  certain  non-contagious  diseases,  such  as  herpes 
zoster,  ulcer  of  the  stomach,  etc.,  during  definite  age  periods; 
(2)  the  fact  that  foci  of  infection  afford  opportunity  for 
bacteria  to  grow  under  varying  grades  of  oxygen  pressure  and 
in  mixed  culture,  both  of  which  have  been  shown  to  cause 
changes  in  virulence  and  other  properties  of  bacteria,  in- 
cluding the  streptococcus  group;  (3)  the  occurrence  of  sys- 
temic infections  such  as  rheumatic  fever,  appendicitis,  ulcer  of 
the  stomach,  etc.,  usually  after  the  acute  symptoms  in  follicu- 
lar tonsillitis  (hemolytic  streptococci)  have  subsided,  and  (1) 
the  finding:  in  the  focus  and  involved  tissues  at  the  time  of  the 
systemic  infection,  streptococci  having  elective  affinity  for  these 
structures  in  animals. 

Since  different  bacteria  may  acquire  simultaneously  affinity 
for  the  same  tissue,  diseases  which  resemble  each  other  more  or 
less  closely,  such  as  the  different  forms  of  arthritis,  may  be  due 
to  bacteria  of  different  species  each  having  elective  affinity  for 
the  particular  structures  involved. 

The  figures  in  the  lowest  line  of  the  table  represent  the  results 
of  numerous  experiments  (833)  with  streptococci  (220)  from 
a  wide  range  of  sources,  and  may  therefore  be  regarded  as  an 
index  of  the  liability  of  the  various  organs  to  infection.  Thus, 
joint  lesions  occurred  more  often  (27  per  cent.)  than  lesions  in 
other  organs,  corresponding  to  the  frequent  occurrence  of  spon- 
taneous arthritis  in  man  and  animals.  The  occurrence  of  le- 
sions in  the  stomach  (20  per  cent.),  valves  of  the  heart  (14  per 
per  cent.),  myocardium  (12  per  cent.)  and  skeletal  muscles  (12 
per  cent.)  correspond  in  a  general  way  to  the  occurrence  of 
infection  in  these  organs  in  man.     The  very  infrequent  involve- 


46  FOCAL  INFECTION 

ment  of  the  skin,  tongue  and  the  parotid  in  the  animals  is  in 
keeping  with  the  rarity  of  embolic  infections  in  these  struc- 
tures. The  character  of  the  lesions  and  their  occurrence  simul- 
taneously in  the  joints,  heart,  muscles  and  kidneys,  and  the 
development  of  chorea  (7  per  cent,  mostly  in  young  rabbits) 
following  injection  of  the  streptococci  from  rheumatic  fever, 
parallels  quite  closely  the  phenomena  of  rheumatic  infection 
as  observed  in  man.  The  strains  from  erythema  nodosum  re- 
semble those  from  rheumatic  fever,  producing  a  relatively  high 
incidence  of  arthritis,  pericarditis  and  myositis,  a  fact  which 
supports  the  view  held  by  clinical  observers,  that  the  causative 
agents  of  rheumatic  fever  and  erythema  nodosum  must  be 
similar. 

The  tendency  to  localize  electively  within  a  limited  range, 
"monotropism,"  is  most  highly  developed  in  the  relatively  non- 
virulent  strains  isolated  from  chronic  lesions.  In  the  more 
virulent  strains  from  acute  lesions  and  after  animal  passage,  this 
tendency  is  less  highly  developed,  the  lesions  occurring  over  a 
wider  range,  "polytropism."  Since  the  bacteria  which  have 
grown  in  a  given  tissue  acquire  greater  affinity  for  this  tissue, 
the  likelihood  of  these  bacteria  to  involve  other  structures  is  rel- 
atively slight;  hence  the  secondary  focus,  a  cholecystitis,  for 
example,  would  appear  to  be  less  important  as  a  distributer  of 
bacteria  than  the  primary  focus ;  if,  however,  the  secondary 
focus  happens  to  be  in  a  joint,  of  which  there  are  many,  it  may 
play  an  important  role  in  causing  extension  to  uninvolved  joints 
and  in  preventing  recovery. 

The  great  importance  of  the  enormous  and  pains- 
taking experiments  and  the  rational  deductions  made 
by  Rosenow  must  be  apparent  to  clinicians,  bacteriolo- 
gists and  pathologists. 

The  practical  application  of  the  principles  involved 
may  serve  to  lessen  the  incidence  of  and  the  recru- 


STREPTOCOCCUS-PNEUMOCOCCUS     47 

descence  of  many  local  inflammatory  organic  diseases, 
notably  appendicitis,  nicer  of  the  stomach  and  duo- 
denum, cholecystitis,  glomerulonephritis,  acute  and 
chronic  arthritis  and  other  abnormal  conditions,  by  the 
removal  of  the  primary  focal  cause. 


LECTURE  III 

ACUTE    DISEASES    RELATED    TO    FOCAL    INFECTION 

We  have  considered  the  causes,  character  and  diag- 
nosis of  focal  infection;  the  mode  of  systemic  infec- 
tion from  the  focus;  the  important  fact  of  transmuta- 
tion within  the  members  of  the  streptococcus-pneumo- 
coccus  group,  with  coincident  variations  of  specific  path- 
ogenicity and  virulency  and  the  acquirement  of 
pathogenic  elective  tissue  affinity  by  bacteria  in  culture 
media,  in  serial  animal  passage  and  in  the  foci  of  in- 
fection. 

We  may  now  understandingly  consider  some  of  the 
systemic  infections  which  are  etiologically  related  to 
focal  infection. 

ACUTE   RHEUMATIC  FEVER 

It  is  not  necessary  to  consider  the  controversies  which 
have  taken  place  concerning  the  bacterial  cause  of  rheu- 
matic fever.  There  is  now  no  doubt  that  the  diplococcus 
also  called  by  other  observers  micrococcus  rheumaticus 
and  streptococcus  rheumaticus,  isolated  from  the  blood 
and  joint  fluids,  throat  and  endocardial  nodes  of  patients 
suffering  from  rheumatic  fever  by  Poynton  and  Paine 
(14)  confirmed  by  Beattie  (15),  Walker  and  Ryffel 
(16)  and  finally  and  conclusively  by  Rosenow  (8),  is 
the  true  infectious  cause  of  the  disease. 

48 


ACUTE  DISEASES  49 

With  a  knowledge  of  the  possibility  of  transmutation 
in  form,  cultural  characteristics  and  coincident  varia- 
tion in  specific  pathogenicity,  virulency  and  tissue  af- 
finity, we  may  now  understand  the  conflicting  results 
of  animal  inoculation  with  undifferentiated  strains  of 
streptococci  as  reported  by  many  workers.  It  is  a  well 
known  fact  that  virulent  strains  of  streptococci,  when 
injected  intravenously  into  animals,  may  produce  acute 
arthritis,  usually  with  such  violent  tissue  reaction  that 
suppuration  occurs.  But  the  streptococcus  rheumati- 
cus  never  produces  suppuration.  Doubt  of  its  etiologic 
relation  to  acute  rheumatism  also  arose  from  the  fact 
that  it  was  not  usually  found  by  cultural  methods  in 
the  joint  exudate  and  circulating  blood  of  patients. 
But  Rosenow  (8)  has  found  that  with  an  improved 
technic  it  may  be  always  found,  at  the  proper  stage 
of  the  disease,  in  the  joint  exudate,  joint  capsule,  cir- 
culating blood,  tonsil,  alveolar  abscess  or  other  focus. 

Rosenow's  studies  of  cultures  from  the  joint  exudate 
of  patients  with  acute  rheumatism  yielded  three  strains. 
From  five  patients  without  muscular  involvement,  on 
blood  agar  the  colonies  were  green  and  grew  in  long 
chains,  longer  than  streptococcus  viridans.  Injected 
intravenously  into  animals  they  developed  acute  non- 
destructive arthritis,  myositis,  marked  myocarditis  with 
endocarditis  and  occasionally  pericarditis.  From  six 
patients  with  acute  rheumatic  fever  involving  the  joints 
and  muscles  the  isolated  microorganisms  produced  slight 
hazy  hemolysis  on  blood  agar,  and  grew  as  diplococci  in 
the  short  chains.  Injected  intravenously  the  inoculated 
animals     developed    non-destructive,     acute    arthritis, 


50  FOCAL  INFECTION 

myositis,  severe  myocarditis,  endocarditis  and  occasion- 
ally pericarditis.  From  three  patients  with  acute  rheu- 
matism the  joint  exudate  yielded  small  gray  colonies 
on  blood  agar.  They  grew  in  clumps  of  small  micro- 
cocci and  diplococci  and  occasionally  in  short  chains. 
Animals  injected  intravenously  developed  a  character- 
istic arthritis  with  endocarditis  and  pericarditis,  but  no 
myositis  or  myocarditis. 

The  three  types  of  cocci  found  by  Rosenow  explains 
the  variations  in  name  given  by  Poynton,  Paine,  Walker 
and  Beattie,  i.  e. :  diplococcus,  streptococcus  and  micro- 
coccus rheumaticus. 

The  virulence  of  all  the  strains  is  low.  All  are  very 
sensitive  to  oxygen  pressure  in  culture  and  all  multiply 
at  low  temperature.  The  three  strains  are  transmut- 
able.  All  produce  excessive  acidity  in  dextrose  broth. 
Walker  and  RyfM  (16)  found  formic  acid  in  the  cul- 
tures of  the  strains  with  which  they  worked. 

Exposure  of  the  inoculated  animal  to  low  tempera- 
ture intensifies  the  disease,  presumably  by  lowering 
phagocytosis  and  by  vasocontraction.  Rosenow  also 
noted  in  some  injected  animals  the  development  of  iritis 
by  hematogenous  infection.  Some  inoculated  animals 
also  developed  appendicitis,  colitis,  mesenteric  lympha- 
denitis and  diarrhea.  Poynton  and  Paine  (14)  also 
have  noted  the  occurrence  of  obscure  infection  of  intes- 
tines and  appendix  of  animals  intravenously  inoculated 
with  the  diplococcus  rheumaticus.  The  intestinal  lesions 
produced  in  animals  and  the  fact  that  the  stool  of  a  pa- 
tient with  rheumatic  fever  may  yield  cultures  of  strepto- 
coccus rheumaticus  indicate  that  the  intestinal  tract  and 


ACUTE  DISEASES  51 

mesenteric  lymph  nodes  may  be  a  secondary  and  pos- 
sibly a  primary  focus  of  rheumatic  fever. 

Rosenow  has  shown  that  cultures  kept  for  one  to 
eight  months  lose  the  power  to  grow  at  a  low  tempera- 
ture, the  sensitiveness  to  oxygen  tension,  the  production 
of  excessive  acid  in  dextrose  broth  and  at  the  same  time 
lose  the  specific  pathogenic  affinity  for  joint,  muscle, 
myocardium,  endocardium  and  pericardium.  By  serial 
animal  passage  the  streptococcus  rheumaticus  and  espe- 
cially the  diplococcus  type,  may  assume  an  affinity  for 
the  appendix,  stomach  and  gall-bladder. 

The  clinical  and  bacteriological  research  of  Poynton 
and  Paine,  the  use  of  blood  agar  media  by  Schottmuller 
to  differentiate  members  of  the  streptococcus  group 
which  are  pathogenic  for  man,  and  the  confirmatory 
work  of  Rosenow  have  proven  conclusively  the  charac- 
ter of  the  infectious  microorganism  which  causes  rheu- 
matic fever  with  arthritis,  myositis,  endocarditis,  myo- 
carditis, pericarditis  and  pleuritis. 

Rheumatic  fever  occurs  most  frequently  in  the  tem- 
perate zone,  among  people  who  live  under  conditions 
which  are  unhealthful  and  which  especially  induce  focal 
infection.  It  is  most  prevalent  in  the  young  and  in 
the  more  exposed  male  of  all  ages.  The  excess  of 
lymphoid  tissue  in  the  pharynx  and  nose  of  the  young 
explains  the  frequency  of  the  incidence  of  the  focal 
infection  and  the  subsequent  rheumatism.  The  fre- 
quent association  of  the  onset  of  rheumatic  fever  with 
lowering  of  the  body  temperature  by  exposure  to  cold 
and  a  wetting  is  explained  by  the  increased  specific 
virulency  of  the  bacterial  cause  acquired  by  a  low  tern- 


52  FOCAL  INFECTION 

perature  and  the  coincident  lessened  resistance  of  the 
patient  due  to  the  exposure.  The  frequent  absence  of 
evidence  of  acute  focal  infection  at  the  onset  of  the 
systemic  disease  is  not  an  evidence  that  no  focus  exists. 
The  latent  chronic  streptococcus  infection  of  tonsillitis, 
pyorrhea  alveolaris,  sinusitis,  etc.,  may  suddenly  acquire 
increased  virulence  and  specific  pathogenic  affinity  with 
varying  degrees  of  focal  tissue  reaction.  This  transmu- 
tation of  type  and  pathogenicity  certainly  occurs  in  the 
focus  of  infection.  The  removal  of  the  tonsils  and  other 
sites  of  focal  infection  has  been  followed  by  complete 
recovery  of  prolonged,  subacute  and  chronic  types 
of  arthritis  and  has  unquestionably  prevented  recurrent 
attacks  of  rheumatic  fever  to  which  the  susceptibility 
is  increased  by  one  or  more  attacks.  The  occurrence  of 
rheumatic  fever  after  the  removal  of  an  apparent  focus 
may  be  due  to  secondary  systemic  latent  foci  in  lymph 
nodes  proximal  to  joints,  in  the  neck  or  elsewhere.  The 
streptococci  of  these  secondary  foci  may  take  on  new 
virulence  and  specific  pathogenicity,  from  the  same 
causes  which  induced  like  changes  in  the  pathogenic 
bacteria  of  the  primary  focus. 

RHEUMATIC  ENDOCARDITIS,  MYOCARDITIS  AND 
PERICARDITIS 

Endocarditis 

We  have  noted  the  fact  that  certain  strains  of  the 
streptococcus  rheumaticus  have  a  greater  affinity  for 
the  endocardium  than  others.  Endocarditis  of  the  rheu- 
matic type  may  be  the  only  recognizable  clinical  entity, 
especially  in  children,  and  may  be  so  mild  that  it  escapes 


ACUTE  DISEASES 


53 


notice.  Later  a  valvular  scar  defect  may  be  manifest. 
In  rheumatic  fever  endocarditis  occurs  most  frequently 
in  children.    After  twenty  years  it  occurs  less  frequently 


Fig.   8. — Subendothelial,    Nodular,   Valvular   and   Mural   Endocarditis 
of  Dog  Following  Injection  of  "Streptococcus  Rheumaticus." 


during  the  first  attack.  The  incidence  of  endocarditis 
increases  with  the  number  of  attacks,  and  always  in 
larger  percentage  in  children. 

As  stated  the  virulence  of  the  streptococcus  rheu- 


54  FOCAL  INFECTION 

maticus  is  low,  compared  with  other  pathogenic  strains 
of  streptococci.  Although  this  relatively  low  virulence 
may  vary  in  degree  and  may  become  high,  the  morbid 
changes  in  joints  and  muscles  consist  at  most  of  hyper- 
emia and  edematous  swelling  of  the  infected  tis- 
sues. The  changes  in  the  endocardium  are  also  char- 
acteristic of  the  usually  mild  virulence  of  the  infectious 
bacteria  as  evinced  by  the  mild  tissue  reaction  in  the 
form  of  small  warty  nodes  of  the  endocardium  and 
valve  segments.  Rarely  is  the  endocarditis  so  severe 
as  to  be  called  ulcerative  or  malignant.  When  that  con- 
dition occurs  a  change  in  type  or  in  specific  patho- 
genicity of  the  invading  streptococci  has  probably  oc- 
curred. Although  rheumatic  valvulitis  is  usually  mild 
and  is  of  itself  rarely  dangerous,  the  secondary  sclerotic 
changes  and  retraction  of  the  segments  is  an  irremedi- 
able and  harmful  sequel. 

Myocarditis 

Myocarditis  is  undoubtedly  a  common  incident  in 
rheumatic  fever  only  recognized  clinically  when  marked 
cardiac  incompetency  occurs  with  or  without  dilatation. 
Mild  myocarditis  alone  due  to  infection  with  strepto- 
cocci which  have  a  pathogenic  affinity  for  muscular  tis- 
sue undoubtedly  occurs  from  chronic  infectious  foci. 
The  mild  reaction  excited  by  the  streptococci  of  low 
virulency  in  the  walls  of  the  heart  is  naturally  in  the 
form  of  proliferative  interstitial  tissue  changes. 


ACUTE  DISEASES  55 

Pericarditis 

Pericarditis  may  occur  alone,  in  association  with  en- 
docarditis, and  may  be  involved  in  pancarditis  in  the 
course  of  rheumatic  fever.  It  may  occur  as  a  simple 
fibrinous  or  serofibrinous  type.  Occasionally  purulent 
pericarditis  may  occur  with  rheumatic  fever  in  chil- 
dren. Pus  in  the  pericardium  or  in  a  joint  would  indi- 
cate a  coincident  infection  with  pyogenic  bacteria  or  a 
change  in  pathogenicity  of  the  infectious  agent, 
for  the  streptococcus  rheumaticus  does  not  cause 
suppuration.  In  rheumatic  fibrinous  and  serofibrinous 
pericarditis,  the  prognosis  is  good  for  recovery,  but 
adhesions  of  the  pericardial  layers  is  a  common  sequel 
which  later  may  cause  nutritional  disturbance  of  the 
heart  muscle. 

CHOREA 

Acute  chorea  is  an  infectious  disease.  Its  casual  re- 
lation with  rheumatic  fever  and  the  frequency  of  endo- 
carditis of  the  simple  rheumatic  type  in  chorea  indicate 
the  infectious  character  and  a  common  bacterial  cause. 
The  incidence  of  the  disease  is  much  the  same  as  rheu- 
matism. The  first  attack  occurs  most  frequently  in 
children  between  the  ages  of  five  and  fifteen  years. 
Seasonal  incidence  is  the  same  as  rheumatism.  An  at- 
tack of  chorea  may  precede,  occur  with  or  follow  an  at- 
tack of  rheumatic  fever.  Recurrent  attacks  usually 
occur.  Pericarditis  may  occur.  Recovery  is  the  rule. 
The  nervous  phenomena,  ataxic  movements,  muscular 
weakness,  mental  disturbances,  mutism,  etc.,  may  occur 
by  hematogenous  infection,  with  a  type  of  the  strepto- 


56  FOCAL  INFECTION 

coccus  rheumaticus  which  has  a  specific  elective  affinity 
for  the  brain.  Multiple  cerebral  bacterial  embolism  due 
to  a  type  of  streptococcus  of  low  virulence  would  cause 
little  anatomical  disturbance,  but  could  be  provocative 
of  all  the  motor  and  sensory  phenomena  of  the  disease. 
Indeed,  gross  embolism  of  the  smaller  cerebral  vessels 
has  been  found  and  has  been  the  source  of  the  etiologic 
embolic  theory.  Simple  verrucose  endocarditis  resem- 
bling simple  rheumatic  endocarditis  is  the  most  common 
morbid  anatomical  change  in  chorea.  The  cerebral 
embolism  theory  is  related  to  the  associated  endocar- 
ditis, with  alleged  detachment  of  small  emboli  composed 
of  fibrin,  blood  cells,  etc.  During  life  one  may  not  study 
the  tissues  of  the  brain  as  in  other  hematogenous  in- 
fections of  muscles,  joints,  lymph  glands,  etc.  The 
discovery  of  bacterial  emboli  in  other  infected  tissues 
of  rheumatic  fever,  and  the  recognition  of  very  slight  re- 
sulting tissue  reaction,  is  presumptive  evidence  that  bac- 
terial cerebral  embolism  may  be  the  cause  of  chorea. 
Rothstein  and  others  have  isolated  strains  of  strepto- 
cocci post  mortem  from  the  meninges  of  choreic  individ- 
uals. Animal  experimentation  with  specific  strains 
of  the4  streptococcus  isolated  in  rheumatic  fever  asso- 
ciated with  chorea  has  been  followed  by  joint  infection 
and  characteristic  symptoms  of  chorea  in  the  inoculated 
animals. 

ACUTE  SYSTEMIC  GONOCOCCUS  INFECTION 

Gonococcemia  may  result  from  a  local  infection 
of  the  prostate,  seminal  vesicles,  joints  and  tendon 
sheaths,  from  infected  thrombi  of  the  veins  contigu- 


ACUTE  DISEASES  57 

ous  to  local  gonococcus  infection  and  also  from  in- 
fected thrombi  of  the  venous  sinuses  of  the  uterus  in 
the  puerperium.  Gonococcemia  is  a  very  serious  con- 
dition, usually  fatal  when  the  cause  of  malignant  endo- 
carditis and  childbed  fever.  Like  other  bacteria  the 
gonococcus  varies  in  degrees  of  virulence,  and  if  mild 
the  patient  may  recover  from  a  gonococcemia  even 
though  the  condition  is  associated  with  endocarditis, 
puerperal  fever  or  suppurative  arthritis.  Thayer  (57) 
has  reported  the  recovery  of  two  cases  of  gonococcus 
endocarditis.  I  have  seen  two  patients  recover  who  had 
suppurating  multiple  arthritis  with  gonococcemia.  All 
of  the  suppurating  joints  were  opened  and  drained, 
which  doubtless  aided  recovery.  The  removal  of  the 
focal  cause  in  all  systemic  gonorrheal  infection  may 
aid  in  overcoming  the  general  disease. 

Gonococcus  Arthritis 

Arthritis  is  the  most  frequent  systemic  expression 
of  gonococcus  focal  infection.  When  monarticular  the 
knee  joint  is  most  frequently  involved.  Males  suffer 
in  the  proportion  of  twelve  to  one  or  two  of  females. 
It  usually  occurs  during  an  acute  gonorrhea,  but  may 
occur  after  the  subsidence  of  an  acute  attack  or  from 
a  long  existing  focal  infection  of  the  genito-urinary 
organs.  For  some  reason  the  latent  bacteria  may  take 
on  new  virulence  and  cause  the  late  systemic  manifesta- 
tion. In  women  the  focal  lesion  may  be  difficult  to 
locate. 

Anatomically  it  occurs  as  a  synovitis,  and  peri- 
arthritis, with  bursitis  and  tenovaginitis.    The  synovial 


58  FOCAL  INFECTION 

joint  effusion  is  usually  serofibrinous  and  occasionally 
purulent.  Purulent  bursitis  and  tenovaginitis  are  more 
frequent.  Periarthritis  of  the  wrist  with  suppuration 
extending  along  the  sheaths  of  tendons  of  the  hands 
may  occur.  Periostitis  of  the  os  calcis  with  resulting 
exostosis  and  marked  tenderness  of  the  heel  is  a  re- 
markable condition  due  to  the  gonococcus. 

The  gonococcus  is  present  in  the  infected  tissues  and 
in  the  exudate  of  the  joints,  bursae  and  tendon  sheaths 
from  which  with  proper  technic  it  may  be  recovered  in 
pure  culture.  In  chronic  conditions  the  infection  may 
be  mixed  with  streptococci  and  staphylococci. 

It  is  a  most  damaging  and  seriously  disabling  disease. 

When  the  exudate  is  purulent,  early  operative  relief 
may  save  the  joint  and  tendon  sheaths  and  preserve 
function.  In  non-purulent  conditions  the  tendency  is 
to  a  long  obstinate  course  with  resulting  damage  to  the 
blood  vessels  of  the  infected  tissues.  This  results  in 
local  malnutrition  with  the  attendant  metabolic  changes 
in  the  joint  and  tendons  with  resulting  deformity  and 
loss  of  function. 

Gonococcus  arthritis  is  often  mistaken  for  rheuma- 
tism. Unlike  rheumatism  it  more  frequently  attacks 
tendon  sheaths  and  the  exudate  is  sometimes  purulent. 
It  may  involve  the  intervertebral,  temporomaxillary, 
sternoclavicular  and  sacro-iliac  joints  while  rheumatism 
rarely  does  so.  Both  may  be  polyarticular.  Gonorrheal 
arthritis  is  often  very  painful  in  undue  proportion  to 
the  apparent  local  infection.  As  a  rule  the  fever  is  not 
high.  The  ordinary  antirheumatic  drugs  do  not  alter 
the  clinical  course.     In  many  instances  the  removal  of 


ACUTE  DISEASES  59 

the  infectious  focus  is  followed  by  quick  relief  of  the 
systemic  disease. 

MALIGNANT  ENDOCARDITIS 

Malignant  or  ulcerative  endocarditis,  so  called  because 
of  the  tendency  to  local  tissue  destruction  and  the  high 
mortality  which  it  causes,  may  be  acute  or  chronic.  It 
is  always  a  secondary  disease.  It  may  be  a  local  com- 
plication of  a  systemic  disease  like  pneumonia,  typhoid 
fever,  epidemic  cerebrospinal  meningitis  and  rarely  of 
rheumatic  fever,  or  it  may  arise  from  a  focal  infection 
anywhere  in  the  body  due  to  the  gonococcus,  strepto- 
coccus, staphylococcus  and  less  frequently  to  other  in- 
fectious bacteria.  There  is  always  an  associated  bac- 
teriemia.  The  bacteria  which  are  most  frequently  found 
in  the  infected  heart  tissues,  vegetations  and  contained 
thrombi,  in  the  blood  stream  by  cultures,  are  strepto- 
cocci, pneumococci,  gonococci  and  staphylococci. 
Streptococci  are  the  most  frequent  cause  and  reach  the 
blood  stream  and  heart  from  septic  wounds,  the  septic 
puerperal  uterus,  and  other  streptococcus  foci  about 
the  head  and  elsewhere.  While  the  streptococcus  py- 
ogenes is  the  strain  which  causes  most  of  the  acute  types 
arising  from  acute  infectious  foci,  the  streptococcus  vi- 
ridans  may  also  cause  the  acute  type,  but  usually  is  the 
cause  of  chronic  malignant  endocarditis. 

Bacteriemia  associated  with  the  general  diseases 
named  or  due  to  a  focal  infection  may  not  involve  the 
heart.  The  normal  endocardium  is  apparently  resistant 
.while  old  sclerotic  processes  of  the  valves  and  congenital 
deformities  of  the  heart  and  proximal  vessels  predis- 


60  FOCAL  INFECTION 

pose  to  malignant  endocarditis.  Hence  malignant  endo- 
carditis most  often  occurs  in  individuals  suffering  from 
chronic  valvular  disease  and  chronic  cardiomyopathy. 


Fig.  9. — Vegetative  and  Ulcerative  Endocarditis  of  Aortic  Valves 
and  Aorta  of  Dog  Following  Injection  of  Streptococcus  Viridans 
from  Chronic  Vegetative  Endocarditis  of  Man. 

The  morbid  anatomy  is  essentially  the  same  in  all  bac- 
terial types  of  the  acute  form.  Usually  vegetations  are 
present,  often  massive,  especially  when  due  to  the  pneu- 


ACUTE  DISEASES 


61 


mococcus,  and  streptococcus  viridans.  Occasionally  the 
vegetations  are  not  large  while  necrotic  destructive 
lesions  are  dominant  in  very  virulent  infections  and  es- 
pecially when  staphylococci  are  the  cause.  From  the  cir- 


.>^:f.-.r ;•;?>- ''/---';  ■ 


-'-'■  %  4 


1  ■»'■:  -f  .    '  'if  .*  *■ 


Fig.    10. — Section    Through    Vegetations   on    Mitral   Valve    Shown    in 
Fig.  9.     Note  the  dark  areas  consisting  of  clumps  of  streptococci. 

culating  blood  thrombus  formation  occurs  in  the  vege- 
tations. Necrosis  of  endocardium,  superficial  and  deep, 
with  perforation  of  valves  and  other  destructive  lesions, 
may  occur.  The  infectious  bacteria  are  present  in  great 
number  in  the  vegetations,  thrombi  and  involved  tis- 
sues. 


62  FOCAL  INFECTION 

When  malignant  endocarditis  occurs  as  a  local  com- 
plication of  a  general  disease  like  pneumonia,  rheu- 
matic fever,  cerebrospinal  fever,  or  some  other  acute 
disease,  it  may  not  be  recognized  because  the  severe 
symptoms  of  the  systemic  disease  may  overshadow  and 
mask  the  manifestations  of  the  local  condition.  As  a 
rule  the  other  symptoms  of  the  general  disease  are  in- 
tensified with  evidence  of  failing  heart,  leading  to  a 
rapid  fatal  issue.  Frequently  the  severe  endocarditis 
is  first  recognized  at  autopsy. 

There  are,  however,  special  and  characteristic  symp- 
toms which  may  lead  to  the  recognition  of  the  condition 
of  the  heart  and  especially  if  a  bacteriemia  is  found  by 
blood  culture.  Detached  small  particles  of  the  vegeta- 
tions and  of  thrombi  carried  in  the  blood  stream  may 
cause  embolism  in  the  various  tissues  and  organs.  Em- 
bolism may  give  rise  to  delirium,  coma,  paralysis,  peri- 
splenitis, with  enlargement  and  tenderness  of  the  spleen, 
varying  degrees  of  hematuria,  gangrene  of  distal  tissues 
and  petechiae,  and  at  any  point  local  abscesses  may  de- 
velop from  the  infected  emboli.  Mycotic  aneurism  may 
result.  Embolism  of  lung  followed  by  abscess  may 
occur  if  the  right  heart  is  involved.  Usually  the  local 
cardiac  disease  is  manifested  by  endocardial  murmurs, 
but  may  be  absent.  The  septic  type  is  marked  by  chills 
and  an  intermittent  or  remittent  type  of  fever  and  severe 
sweats.  A  typhoid  type  is  characterized  by  a  more  con- 
tinued type  of  fever,  delirium,  coma  and  rapid  course. 
In  rare  instances  the  clinical  picture  is  that  of  cerebro- 
spinal meningitis.  The  diagnosis  may  be  difficult,  but 
is  greatly  aided  by  blood  culture. 


ACUTE  DISEASES 


63 


Malignant  endocarditis  usually  terminates  fatally,  but 
recovery  has  been  noted  by  Herrick  (21)   and  others 
In  coroner's  autopsy  cases  E.  R.  LeCount  has  recog- 
nized six  or  more  instances  of  healed  scars  of  ulcerative 
endocarditis. 

ACUTE   NEPHRITIS 

The  types  of  acute  infectious  nephritis  which  usually 
rises  from  a  focal  infection  is  embolic  because  the  mode 


Fig.  11.— A  Glomerulus  Containing  a  Hyaline  Thrombus.  From  a 
rabbit  dying  7  days  after  inoculation.  X  275  (after  LeCount  and 
Jackson,  Jour.   Inf.   Dis.). 

of  infection  is  hematogenous.    It  is,  therefore,  primarily 
a  glomerulonephritis.    If  the  dose  of  infectious  bacteria 


64 


FOCAL  INFECTION 


reaching  the  kidney  is  large  enough,  the  nephritis  may 
be  diffuse.  Usually  the  condition  is  expressed  clinically 
by  bloody  urine  of  varying  degree,  microscopic  blood 
is    present    with    albuminuria    and    casts    of    various 


Fig.   12. — Masses  of  Fibrin  in  a  Glomerulus.     From  rabbit  dying  7  days 
after  injection.  X  200   (after  LeCount  and  Jackson,  Jour.  Inf.  Dis.). 


types.  The  urine  is  lessened  in  quantity  in  twenty- 
four  hours,  soon  a  secondary  anemia  develops  and 
often  within  a  short  period  a  soft  edema.  Varying  de- 
grees of  this  type  of  nephritis  occur  from  focal  infec- 
tion. The  most  usual  site  of  the  focal  infection  which 
causes  the  nephritis  is  the  throat.    In  the  milder  types 


ACUTE  DISEASES  65 

of  this  form  of  nephritis  apparent  complete  resolution 
occurs  after  the  removal  of  the  focus  of  infection.  Bill- 
ings (9)  has  reported  clinical  observations  on  the  rela- 
tion of  focal  infection  to  glomerulonephritis   and  the 


Fig.  13. — A  Glomerulus  ik  Which  Are  Masses  of  Cocci  Filling  a  Group 
of  Capillaries.  From  a  rabbit  dying  9  days  after  inoculation.  X  325 
(after  LeCount  and  Jackson,  Jour.  Inf.  Dis.). 

apparent  resolution  of  the  infection  of  the  kidneys  by 
eradication  of  the  focus.  LeCount  and  Jackson  (35) 
have  shown  the  renal  changes  in  rabbits  inoculated  with 
streptococci.  Of  these  animals  six  were  inoculated  with 
strains  of  streptococci  isolated  from  patients  with  epi- 
demic septic  angina.    The  kidney  lesions  were  primarily 


66  FOCAL  INFECTION 

of  the  vascular  structures,  glomeruli,  intertubular  ves- 
sels and  arcuate  and  interlobar  veins.  They  noted  a 
pronounced  perivascular  exudate  consisting  chiefly  of 
lymphocytes  and  plasma  cells.  The  tendency  to  repair 
in  the  acute  glomerular  lesion,  noted  by  LeCount  and 
Jackson,  is  very  important  when  compared  with  the 
tendency  to  recovery  of  clinical  glomerulonephritis  of 
man,  when  the  chief  etiologic  factor  is  removed. 

ACUTE  APPENDICITIS 

Acute  appendicitis  due  to  focal  infection  located  in 
the  throat  and  nose  and  sometimes  in  the  jaws  has  been 
noted  by  a  great  number  of  clinical  observers,  notably 
among  the  French.  Kretz  (25)  has  shown  the  frequent 
infection  of  the  cervical  lymph  nodes  with  streptococci. 
When  the  cause  of  the  lymphogenous  infection  is  acute 
Kretz  believes  that  the  bacteria  filtrate  rapidly  through 
the  lymph  nodes,  with  resulting  severe  bacteriemia.  In 
less  severe  types  of  focal  infection  of  the  head  and  in 
adults  especially,  the  virulence  and  degree  of  bac- 
teriemia is  usually  less.  In  these  conditions,  local  or 
general  systemic  infection  may  follow  in  the  form  of 
acute  multiple  arthritis  (rheumatism),  endocarditis, 
pericarditis,  osteomyelitis,  nephritis,  appendicitis, 
cholecystitis  and  even  streptococcus  malignant  endo- 
carditis. He  also  believes  that  acute  appendicitis  and 
cholecystitis  are  hematogenous  in  origin  and  never  pri- 
marily caused  by  infection  within  the  lumen  of  the  ap- 
pendix and  gall-bladder.  Cannon  (26)  argues  that 
appendicitis  and  cholecystitis  are  hematogenous  infec- 
tions, and  may  be  of  focal  origin.     He  believes  that 


ACUTE  DISEASES  67 

typhoid  cholecystitis  occurs  through  the  blood  stream. 

After  animal  experimentation  and  a  study  of  the 

tissues  and  bacteria  of  appendicitis,  Ghon  and  Namba 


Fig    14. — Marked  Hemorrhage  of  the  Appendix  24  Hours  After  Injec- 
tion of  Streptococci  from  Tonsils  in  a  Case  of  Human  Appendicitis. 

(27)  conclude  that  if  appendicitis  occurs  hematogenous- 
ly  it  must  be  due  to  a  specific  strain  of  streptococci. 

Adrian  (28)  has  observed  appendicitis  as  a  focal  in- 
fection of  general  disease.  He  apparently  considers 
the  bacteriemia  of  a  focal  infection  a  general  disease. 


68 


FOCAL  INFECTION 


Hence  he  cites  clinical  observation  of  angina,  with  ap- 
pendicitis. He  very  fully  reviews  the  literature  quoting 
the  opinion  of  many  German,  French  and  a  few  Amer- 


Fig.  15. — Hemorrhage  and  Localized  Infection  of  Mucous  Membrane 
of  Duodenum  and  Tip  of  Appendix  48  Hours  After  Injection  of 
Streptococcus  from  Human  Appendicitis  After  Three  Animal 
Passages. 


ican  clinicians  upon  the  relation  of  angina  to  appendi- 
citis and  rheumatism.  The  histologic  lymphoid  struc- 
ture of  the  tonsils  and  appendix  is  compared  and  the 
similarity  of  tissue  is  given  as  a  reason  for  the  etiological 


ACUTE  DISEASES 


69 


relation  of  the  angina  to  appendicitis.  The  term 
"anginal  appendicitis"  has  been  coined  to  express  this 
relation. 

The  confirmatory  investigations  of  Rosenow  ( 8 )  have 
shown  the  occurrence  of  acute  appendicitis  from  strains 


tifc 


■ym 


Fig.    16. — Human   Appendicitis    12   Hours   After   Onset   in   Young  Man. 
Note  the  necrosis  and  infiltration  of  lymph  follicles. 

of  streptococci,  colon  bacilli  and  other  organisms  which 
have  attained  elective  affinity  for  the  tissues  of  the 
appendix.  This  elective  tissue  affinity  has  been  acquired 
by  these  microorganisms  in  the  tissues  of  the  appendix 
during  an  attack,  for  when  they  are  isolated  from  the 


70 


FOCAL  INFECTION 


infected  tissues  of  the  appendix  and  nascent  cultures 
are  injected  intravenously  into  animals,  acute  appendi- 
citis occurs  in  the  great  majority  of  the  inoculated 
animals.  The  same  affinity  for  tissues  of  the  appendix 
can  be  induced  to  appear  in  strains  through  variations 
in  culture  methods  and  serial  animal  inoculation. 


Fig.  17. — Diplococci  in  Peritoneal  Coat  of  Appendix  Shown  in  Fig.  16. 


The  invading  organisms  reaching  the  tissues  of  the 
appendix  hematogenously  cause  small  hemorrhages  in 
the  walls  of  the  organ  and  if  this  invasion  is  great 
enough  the  reaction  of  the  tissues  to  the  invading 
organisms  causes  a  positive  chemotaxis  with  invasion 
of  leukocytes  and  plasma  cells  and  consequent  tumefac- 
tion of  the  tissues  and  obstruction  of  the  canal  of  the 
appendix.  With  obstruction  there  occurs  a  condition 
which  invites  the  rapid  increase  in  the  numerous  sapro- 
phytic anaerobes  and  other  bacteria  usually  present  in 


ACUTE  DISEASES 


71 


the  bowel  and  appendix  with  resulting  increase  of  mor- 
bid tissue  change,  varying  in  degree  from  edema  to 
necrosis  and  gangrene.  Until  these  investigations  of 
Rosenow,  the  presence  of  colon  bacteria  and  of  various 


Fig.  18. — Hemorrhage  Necrosis  and  Leukocytic  Infiltration  20  Hours 
After  Injection  of  Streptococcus  from  Appendix  in  Human  Ap- 
pendicitis After  One   Animal  Passage. 


other  saprophytic  organisms  in  the  tissues  of  the  normal 
as  well  as  the  infected  appendix,  has  led  to  the  belief 
that  acute  appendicitis  has  been  excited  by  an  infection 
within  the  bowel  by  the  various  saprophytic  organisms 
usually  found  there.    This  secondary  invasion  of  anae- 


72 


FOCAL  INFECTION 


'  ■     •      ** 


'*      *%* 


«    .  %  V  * 


Fig.   19. — Streptococci  in  Lymph  Follicle  Shown  in  Fig.  18  of  Appen- 
dix 20  Hours  After  Injection  of  Streptococci. 

robes  and  other  bacteria  often  found  in  the  tis- 
sues closely  related  to  the  intestinal  tract  have  been  de- 
scribed as  the  primary  causes  of  appendicitis  by  Heyde 
(29),  Aschoff  (30)   and  others.     The  argument  from 


Fig.    20. — Streptococci    and    Fusiform    Bacilli    in    Human    Gangrenous 
Appendicitis  Following  Vincent's  Angina. 


Fig.  21. — Hemorrhage,  Necrosis  and  Leukocytic  Infiltration  of  Appen- 
dix 24  Hours  After  Injection  of  Mixed  Culture  of  Fusiform  Ba- 
cilli and  Streptococci  from   Human  Appendix  Shown  in   Fig.  20. 


Fig.    22. — Streptococci    and    Fusiform    Bacilli    of    Appendix    of    Rabbit 
Shown  in  Fig.  21  24  Hours  After  Intravenous  Injection. 

73 


74 


FOCAL  INFECTION 


this  point  of  view  is  that  these  facultative  bacteria  in- 
vade the  tissues  from  the  lumen  of  the  bowel,  when  the 
resistance  of  the  body  tissues  is  low,  and  especially  when 
the  lumen  of  the  appendix  is  partly  or  wholly  closed 
by  fecal  concretions,  kinks  of  the  organ  or  from  other 
causes.    The  more  reasonable  relation  of  these  bacteria 


% 

* 

V 

1 

1 

t 

\ 

- 

« 

* 

0 

% 

* 

1    V 

c 

%.. 

0 

Fig.  23. — Photomicrograph  of  24  Hour  Culture  in  Ascites-Dextrose- 
Broth  of  a  Streptococcus  Isolated  from  a  Gall-bladder  in  Human 
Cholecystitis.  The  morphology,  size  and  grouping  are  quite  typical 
of  strains  from  cholecystitis.     Gram  stain. 


to  the  disease  is  that  of  a  mixed  infection,  secondary  to 
the  primary  hematogenous  invasion  usually  by  strepto- 
cocci. 

How  much  the  lessened  resistance  of  the  tissues 
of  the  appendix  due  to  the  presence  of  fecal  stones  and 
other  foreign  bodies  or  to  kinking  of  the  organ  may 
have  to  do  in  attracting  the  streptococci  in  the  blood 
stream  to  the  appendix,  needs  further  investigation. 


ACUTE  DISEASES 

CHOLECYSTITIS 


75 


Cholecystitis  is  unquestionably  due  at  times  to  hema- 
togenous infection  with  strains  of  streptococci  and  pos- 


Fig.  24. — Hemorrhagic  Cholecystitis  in  Dog  48  Hours  After  Intrave- 
nous Injection  of  Streptococcus  Shown  in  Fig.  23,  from  the 
Thickened  and  Infiltrated  Wall  of  Human  Gall-bladder  Soon 
After  Isolation. 

sibly  to  other  microorganisms.  A  patient  in  the  Pres- 
byterian Hospital  who  suffered  from  an  attack  of  acute 
cholecystitis  was  operated  and  it  was  noted  that  in  the 


76  FOCAL  INFECTION 

fundus  of  the  gall-bladder  there  was  a  small  softened 

•area  which  was  excised.  The  gall-bladder  also  contained 

some  small  soft  concretions  of  bile.    From  the  softened 


Fig.  25. — Marked  Edema  of  Gall-bladder  in  Dog  24  Hours  After  In- 
travenous Injection  of  a  Streptococcus  from  Duodenal  Ulcer  After 
One  Animal  Passage. 

tissues  of  the  gall-bladder  Rosenow  isolated  a  strain 
of  streptococci  which  injected  into  animals  produced 
cholecystitis.  This  patient  suffered  from  tonsillitis  and 
a  short  period  before  the  onset  of  the  attack  of  cholecys- 


ACUTE  DISEASES 


77 


titis  had  suffered  from  an  acute  tonsillitis.  Strains  of 
the  streptococci  isolated  from  the  tonsil  had  a  like  af- 
finity for  the  gall-bladder  in  intravenously  inoculated 
animals. 

Rosenow  has  shown  also  that  strains  of  the  strepto- 
cocci attain  an  affinity  for  the  gall-hladder  similar  to 


Fig.   26. — Streptococci  in   Lymph   Space    of   Edematous   Wall   of   Gall- 
bladder Shown  in  Fig.  25.     Gram-Weigert  stain. 


that  attained  for  other  tissues,  and  that  this  affinity  may 
be  lost  and  regained  by  varying  methods  of  culture  and 
by  serial  animal  passage. 

There  can  be  no  question  that  cholecystitis  may  occur 
through  hematogenous  infection  by  typhoid  bacilli  and 
probably  by  other  pathogenic  microorganisms,  but  the 
more  frequent  presence  of  streptococci  than  the  other 
pathogenic  bacteria  in  the  center  of  gall-stones  removed 
from  patients,  as  shown  by  Rosenow,  is  suggestive  of 


78 


FOCAL  INFECTION 


the  more  frequent  occurrence  of  streptococcus  cholecys- 
titis. 

ACUTE  GASTRIC  AND  DUODENAL  ULCER 

Acute  peptic,  gastric  and  duodenal  ulcer  may  be  pro- 
duced  experimentally  in   animals   by  the  intravenous 


Fig.  27. — Photomicrograph  of  24  Hour  Ascites-Dextrose-Broth  Culture 
of  Streptococcus  from  Human  Ulcer  at  the  Time  the  Strain 
Proved  to  Have  the  Affinity  for  the  Stomach  When  Intrave- 
nously Injected  Into  Animals.     Grain  stain. 


injection  of  strains  of  streptococci  which  have  an  elec- 
tive affinity  for  the  stomach  wall  and  Rosenow  has 
isolated  this  strain  from  the  base  of  the  ulcer  and  tissue 
of  the  stomach  wall  of  man.  The  strain,  so  isolated, 
proved  to  have  an  elective  affinity  for  the  stomach  wall 
in  animals  intravenously  inoculated.    The  mode  of  pro- 


Fig.  28. — Marked  Ulceration  of  Stomach  in  Guinea  Pig  24  Hours  After 
Intravenous  Injection  of  Streptococcus  from  Suppurating  Frontal 
Sinus  of  Man  with  Stomach  Ulcer. 


Fig.  29. — Photomicrograph  24  Hour  Ascites-Dextrose-Broth  Culture 
of  a  Streptococcus  from  Blind  Abscess  of  Jaw  in  Man  Suffering 
with  Chronic  Ulcer  of  Stomach.  This  strain  proved  to  have  an 
affinity  for  the  stomach  when  intravenously  injected  into  animals. 
Gram  stain. 


79 


Fig.  31. — Capillary  Filled  with  Diplococci  ik  the  Apex  of  the  Ulcer 
Shown  ik  Fig.  30. 

80 


:*?* 


<**•**• 


Fig.  32. — Section  of  Wall  of  Stomach  of  Rabbit  Showing  WEDGE^ 
Shaped  Area  of  Infiltration,  Hemorrhage  and  Beginning  Ulcera- 
tion 48  Hours  After  Intravenous  Injection  of  Streptococci  from 
Tonsil  of  Patient  with  Herpes  Zoster  After  One  Animal  Passage. 


81 


82 


FOCAL  INFECTION 


duction  of  the  ulcer  as  noted  animals  is  a  strepto- 
coccus embolic  infection  of  the  submucosa  of  the  stom- 
ach with  resulting  small  hemorrhages  into  the  surround- 
ing tissues.    In  consequence  of  the  hemorrhage  and  the 


Fig.  33. — Streptococci  at  Apex  of  Wedge-Shaped  Area  Shown  in  Fig.  32. 


presence  of  the  infectious  microorganisms  in  the  sur- 
rounding tissues,  anemic  necrosis  so  weakens  the  over- 
lying mucous  membrane  that  it  becomes  digested  by  the 
gastric  juice.  If  the  necrosis  involves  a  vessel  of  suffi- 
cient size,  visible  stomach  hemorrhage  may  occur.  If 
the  infection  and  injury  is  not  great,  healing  takes  place. 
If  the  infection  is  more  virulent,  chronic  ulcer  results. 


ACUTE  DISEASES 


83 


ACUTE  PANCREATITIS 


Acute  pancreatitis  of  serious  degree  always  requires 
surgical  interference.     When  it  is  of  mild  degree  sur- 


Fig.  34. — Hemorrhagic   Pancreatitis  nsr  Dog  24   Hours  After   Ixjectiox 
of  Streptococcus  from  Stexo's  Duct  est  a  Case  of  Epidemic  Parotitis. 

gical  interference  is  not  usually  required,  but  if  it  be- 
comes a  chronic  condition  degenerative  changes  may 


Fig.  35. — Section  of  Pancreas  in  Dog  Showing  an  Irregular  Staining 
of  Parenchymatous  Cells  and  Thrombosis  of  Blood  Vessels  Two 
Weeks  After  Intravenous  Injection  of  Streptococci  from  Rheu- 
matism. 


84 


ACUTE  DISEASES 


85 


lead  to  involvement  of  the  islands  of  Langerhans  with 
disturbed  function  and  diabetes  mellitus  may  result. 

There  is  a  relation  more  or  less  close  between  the 
strains  of  streptococci  which  have  an  elective  tissue  af- 


Fig.  36. — Photomicrograph  Showing  DiploCocci  in  Area  of  Round  Cell 
Infiltration  Near  a  Partially  Thrombosed  Blood  Vessel  of  Fig.  35. 


finity  for  the  appendix,  gall-bladder,  stomach  wall  and 
pancreas  and  this  has  been  beautifully  and  graphically 
shown  in  the  table,  which  was  presented  in  Lecture  II. 


ERYTHEMA  NODOSUM 

Erythema  nodosum  has  been  recognized  as  a  condi- 
tion which  may  occur  with  acute  or  subacute  rheuma- 
tism or  as  a  part  of  the  syndrome  described  by  Osier 
(17).  The  syndrome  consists  usually  of  polymorphic 
skin  lesions,  hyperemia,  edema,  hemorrhage,  quite  fre- 
quently associated  with  arthritis.     At  times  there  may 


>  •  J 


■■■). 


Fig.  37. — Subcutaneous  Tissues  from  Erythema  Nodosum  in  Man.  Sec- 
tions showing  a  leukocytic  and  round  cell  infiltration  along  tissue 
strands  between  the  layers  of  fat. 


86 


Fig.  38. — Subcutaneous  Tissue  from  Erythema  Nodosum  in  Max.  Sec- 
tion showing  red  blood  corpuscles,  blood  pigment,  nuclei  of  disinte- 
grated leukocytes   and   diplococci   and   diphtheroid   bacilli. 


Fig.  39. — Smear  from  Single  Colony  in  Ascites-Dextrose-Agar  72  Hours 
After  Inoculation  with  the  Emulsion  of  the  Subcutaneous  Node 
Showing  Diphtheroid  Bacilli  in  Fig.  38. 


87 


88 


FOCAL  INFECTION 


be  visceral  crises,  especially  gastro-intestinal,  endocar- 
ditis, pericarditis,  hematuria,  nephritis,  nodose  erythema 
and  peliosis  rheumatica.  The  present  knowledge  of 
the  infectious  nature  of  rheumatism,  of  endocarditis, 
pericarditis  and  nephritis,  point  to  a  probable  focal  in- 
fection as  the  cause  of  the  syndrome,  which  has  been 


Fig.  40. — Smear  from  Blood  of  Guinea  Pig  Injected  with  Culture 
Shown  in  Fig.  39  After  One  Animal  Passage.  Note  the  typical 
diplococci  in  chains. 

discussed  by  clinicians  in  the  past,  as  infectious,  toxic 
or  metabolic. 

The  discovery  of  bacteria  belonging  apparently 
to  the  members  of  the  streptococcus-pneumococcus 
group  in  fresh  tissues  isolated  from  the  nodes  removed 
surgically  from  patients  and  the  production  of  erythema 
nodosum  in  the  skin  of  animals  intravenously  injected 
with  the  cultures  so  obtained,  has  been  demonstrated 
many  times  by  Rosenow. 

The  removal  of  the  apparent  focus  of  infection  in 


Pig.  41. — Photograph  Showing  Circumscribed  Hemorrhages  of  the  Skin 
and  Symmetrical  Hemorrhages  of  the  Fascia  of  the  Inner  Aspect 
of  the  Legs  of  a  Rabbit  48  Hours  After  an  Intravenous  Injection 
of  Culture  of  Diphtheroid  Bacteria  Shown  in  Fig.  39,  Obtained 
from  an  Erythematous  Node  in  Man. 


89 


-;  • '  y$& 


- 
#■  ■•.'■•  •-'•'. 

v*   <     '  >v  i    <     ' 


*c 


asfffe 


4   ">)*!.■?>.. 


Fig.  42. — Section  of  Skin  of  Rabbit  Showing  Hemorrhage  and  Leu- 
kocytic and  Round  Cell  Infiltration  of  Subcutaneous  Tissue  72 
Hours  After  Intravenous  Injection  of  the  Diphtheroid  Bacilli, 
Shown  in  Fig.  39.  Note  the  complete  absence  of  involvement  of  the 
cutis  and  only  slight  infiltration  of  the  corium. 


90 


■       *• 

*&w+ 

k 

Fig.  43. — A  Diflococcus  in  the  Area  of  Infiltration-   Shown-  in   Fig.  42. 


fc%.;Si 


Fig.  44. — Section  of  the  Artery  from  the  Area  of  Subcutaneous  Hem- 
orrhage Shown  in  Fig.  42.    Note  the  mural  aggregation  of  leukocytes. 

91 


Fig.  45. — Diplobacilli   in  the   Wall   of   Artery   Shown   in    Fig.   44. 


*         •  }     *     •• 


/     * 


.  *      * 


Fig.  46. — Photomicrograph  of  24  Hour  Culture  in  Ascites-Dextrose- 
Broth  of  a  Streptococcus  Isolated  from  the  Spinal  Fluid  of  a  Rab- 
bit Which  Showed  Herpes  After  the  Intravenous  Injection  of 
Streptococcus  Culture  from  the  Tonsil  of  a  Man  Who  Suffered 
with  Herpes  Zoster.  The  morphology  is  quite  characteristic  of  the 
strains  from  herpes  zoster. 

92 


Fig.  47. — Herpes  as  Seen  on  Under  Surface  of  the  Skin  Over  the  Lower 
Right  Thoracic  Region  of  a  Rabbit  24  Hours  After  an  Intrave- 
nous Injection  of  Streptococcus  Shown  in  Fig.  46. 


93 


94 


FOCAL  INFECTION 


patients  at  the  Presbyterian  Hospital,  suffering 
from  erythema  nodosum,  has  been  followed  with  relief 
over  periods  of  sufficient  length  of  time  to  clinically 
prove  the  etiologic  relations  of  the  focus  of  infection 
to  the  systemic  condition. 

HERPES 

It  has  long  been  known  that  herpetic  eruptions  may 
be  induced  in  animals  and  that  like  lesions  occur  in  man 


Fig.  48. — Diplococci  in  the  Hemorrhagic  Spinal  Ganglion  Correspond- 
ing with  the  Area  of  Herpes  Shown  in  Fig.  47.   Gram-Weigert  stain. 


from  injury  or  infection  of  the  ganglia  on  the  sensory 
root  of  the  cranial  and  of  the  spinal  nerves.  That  herpes 
zoster  may  be  the  result  of  specific  infection  of  the 
ganglia  of  the  posterior  roots  of  the  spinal  nerves  and 
the  etiologic  infectious  microorganisms  may  be  isolated 
from  the  infected  tonsils  and  other  foci  has  been  dem- 
onstrated with  patients  in  our  clinic.    With  these  strains 


Fig.  49. — Herpes  of  the  Skin  or  the  Inner  and  Upper  Aspect  of  Right 
Thigh  of  a  Rabbit  48  Hours  After  Intravenous  Injection  of  Strep- 
tococcus from  the  Tonsil  of  a  Patient  Suffering  with  Herpes 
Zoster. 


95 


Fig.  50. — Thrombosis  of  a  Vein  (a)  and  Paravascular  Infiltration  (b) 
of  the  Posterior  Spinal  Root  Adjacent  to  the  Ganglion  Within 
the  Dura  Corresponding  to  the  Area  of  Herpes  Shown  in  Fig.  49. 


96 


Fig.  51. — Diplococci  in  Leukocytes  Within  a  Thrombosed  Vein  Shown 
in  Fig.  50.    Gram-Weigert  stain. 


Fig.  52. — Diplococci   in   Hemorrhagic  and  Infiltrated  Area  Shown  in 
Fig.  53.     Gram-Weigert  stain. 


97 


*v».  V 


- 


a 


* 


Fig.  53. — Marked  Hemorrhage  (a)  and  Leukocytic  Infiltration  (b) 
Surrounding  the  Lumbar  Nerve  Just  Outside  the  Spinal  Canal 
Corresponding  to  the  Area  of  Herpes  Shown  in   Fig.  49. 


98 


Fig.  54. — Herpes  of  Tongue,  Mucous  Membrane  About  Teeth  and  Lips 
of  Rabbit  24  Hours  After  Intravenous  Injection  of  Streptococcus 
from  the  Tonsil  in  Recurring  Herpes. 


99 


Fig.  55. — Herpes  of  Skin  of  Left  Side  of  Face  of  a  Rabbit  72  Hours 
After  an  Intravenous  Injection  of  Streptococcus  from  the  Tonsil 
in  Herpes  Zoster. 


100 


4  i 

.  . .  .  v 


lliiifff 


?»>,'vi.''.' 


'■<-.. 


'';W*iH8&ik 


-> 


Fig.  56. — Hemorrhage  (a)  and  Round  Cell  Infiltration  (b)  of  the 
Gasserian  Ganglion  of  Dog  with  Marked  Herpes  of  the  Lip  48 
Hours  After  an  Intravenous  Injection  of  Streptococcus  from  the 
Tonsil  in  a  Patient  with  Lobar  Pneumonia  and  Marked  Herpes  of 
the  Lip  and  Cheek. 


101 


102  FOCAL  INFECTION 

of  the  isolated  bacteria,  herpes  zoster  has  been  produced 
in  intravenously  injected  animals  and  the  streptococci 
have  been  recovered  from  the  posterior  root  ganglia  of 
the  inoculated  animals. 

SPINAL  MYELITIS 

A  recent  interesting  clinical  observation  and  its  re- 
lated laboratory  experiments  as  made  by  Rosenow  is 
worthy  of  record.  A  young  man  suffered  for  three 
years  from  the  mild  but  typical  symptoms  of  spinal  in- 
sular sclerosis.  When  he  was  admitted  to  the  hospital, 
he  suffered  from  ataxia  of  gait  and  station,  greatly  in- 
increased  knee  kicks,  slight  nystagmus,  but  no  intention 
tremor,  and  his  spinal  fluid  was  negative  both  as 
to  abnormal  cells  and  the  serum  tests.  He  had 
periods  of  improvement  and  of  worse  conditions 
associated  with  marked  vertigo  and  falls  without 
unconsciousness.  He  had  suffered  from  chronic  ton- 
sillitis for  years.  With  a  consideration  of  the  possi- 
bility of  a  relation  of  focal  infection  to  the  condition  and 
as  no  other  site  of  infection  could  be  located,  the  tonsils 
were  enucleated.  The  streptococci  isolated  from  the  ton- 
sillar tissue,  chiefly  a  strain  of  the  green  forming  type, 
was  intravenously  injected  into  two  dogs.  In  both 
animals  focal  hemorrhages  were  produced  in  the  spinal 
cord  and  the  development  of  ataxic  gait  and  partial  loss 
of  power  in  all  four  extremities.  From  the  focal  soft- 
ened areas  of  the  spinal  cord  a  like  strain  of  strepto- 
cocci was  recovered. 

The  infectious  etiology  of  focal  hemorrhage  and  soft- 
ening of  the  cerebrospinal  axis  has  been  recognized  for 


ACUTE  DISEASES  103 

a  long  time.  The  possibility  that  the  condition  may 
arise  from  a  focus  of  infection  is  suggested  by  the  ob- 
servation and  experiment  just  mentioned. 

ACUTE  OSTEOMYELITIS 

Acute  osteomyelitis  is  often  ascribed  to  injury  usually 
involving  the  extremities.  There  can  be  no  question 
that  the  infectious  organisms,  usually  tubercle  bacilli, 
streptococci  and  staphylococci,  gain  entrance  into  the 
blood  stream  from  foci  in  the  head  or  lymph  nodes  and 
that  under  certain  conditions  of  increased  virulence  and 
of  lessened  resistance  upon  the  part  of  local  tissues  due 
to  injury  of  the  bones,  single  or  multiple  osteomyelitis 
may  occur.  Kretz  (25)  records  clinical  observation  in 
support  of  the  focal  origin  of  osteomyelitis. 

THYROIDITIS 

Thyroiditis  is  probably  a  much  more  frequent  event 
than  has  been  heretofore  noted.  I  have  already  called 
attention  to  the  frequency  with  which  thyroiditis  occurs 
in  rheumatism.  Vincent  (31)  has  shown  the  incidence 
of  50  to  80  per  cent,  of  swelling  and  tenderness  of  the 
thyroid  gland  in  the  course  of  acute  rheumatic  fever. 
There  can  be  no  question,  too,  that  infection  of  the 
gland  occurs  in  other  general  infections.  It  also  occurs 
from  focal  infection  about  the  mouth,  throat,  and  nose. 
We  have  observed  many  instances  of  thyroid  enlarge- 
ment, usually  of  chronic  type,  associated  with  evidences 
of  thyroid  intoxication  in  many  young  women  patients 
with  focal  infection  in  the  form  of  alveolar  abscess,  ton- 
sillitis and  sinusitis. 


^^«r<^r"•*>,4 

■ 
*  t .                *•  **  t  Mm. 

■*■■■'<;.  '  j^83| 

jMS'M'liUlAi.HLiM .  '"'^  •-  "  - 

2HS^^S|8|<iita?'  -i**  - :, 

•^ 

^Pm^lfP^lPrSl^vi 

wpt^^*^H&.^ 

' 

"*'>:''-  . 

•"■afc*?*""  -*~*S  t.^ 

PR| 

Siu'^S^N 

"'-.  * 

cT<5 

:  .*»T^SI^^B?*5^5J5> 

<*-^viT!*\!? 

•""^.jS^'    -'■l#i&»»        ""^ifcli           ~^ftff_P^,.. 

1  tW^^^^^-^3^^^ 

^wflWllPH         ■!&&:■**              V^ 

^r         «                 ^1 

Fig.  57. — Section  of  Iris  and  Ciliary  Body  of  Rabbit  Showing  Marked 
Leukocytic  Infiltration  (a)  4  Days  After  Intravenous  Injection 
of  Streptococci  from  Rheumatic  Fever. 


104 


ACUTE  DISEASES 


105 


IRIDOCYCLITIS 


Iritis  is  not  an  unusual  event  in  rheumatism,  syphilis 
and  some  other  general  infectious  diseases.  When 
acute  or  subacute  iritis  occurs  alone  the  cause  has  been 
ascribed  to  infection,  toxins,  anaphylaxis  and  to  faulty 


Fig.  58. — Photomicrograph    of    Streptococci    in    Area    of    Infiltration 
Shown  in  Fig.  57.     Gram-Weigert  stain. 

metabolism.  That  infection  plays  a  much  more  constant 
part  in  the  causation  of  iritis  is  apparent  from  the  expe- 
rimental work  of  Rosenow  (8),  Irons  and  Brown  and 
others.  Strains  of  streptococci  in  foci  of  infection 
of  the  teeth,  tonsils  and  sinuses  have  an  unquestionable 
relation  to  iridocyclitis  alone  as  well  as  when  the 
eye  infection  is  associated  with  rheumatic  fever,  chorea, 
syphilis  and  other  acute  general  diseases. 


Fig.  59. — Localized  Hemorrhages  (a)  in  the  Sclera  Near  the  Limbus 
and  at  the  attachment  of  the  external  rectus  muscle  of  rabbit 
48  Hours  After  Intravenous  Injection  of  Streptococci  from  Pus 
Pocket  of  Tonsil. 


Fig.  60. — Diplococcus  Adjacent  to  Area  of  Hemorrhage  Shown  in  Fig. 
59. 

106 


LECTURE   IV 

CHRONIC  DISEASES  RELATED  TO  FOCAL  INFECTION 
CHRONIC  INFECTIOUS   ARTHRITIS 

Under  the  classification  of  chronic  infectious  arthritis 
our  present  knowledge  justifies  the  consideration  of 
chronic  arthritis  which  may  be  due  to  various  forms  of 
pathogenic  bacteria.  Investigation  has  shown  that  a 
strain  of  the  streptococcus,  gonococcus,  tubercle 
bacillus,  bacillus  typhosus  and  spirochete  pallida  are 
the  most  common  infectious  causes  of  chronic  arthritis. 
When  other  bacteria  are  found  in  the  infected  tissues 
of  chronic  arthritis  and  myositis,  they  may  have  etiologic 
relations  to  the  condition,  but  are  probably  present  in 
the  tissues  as  a  mixed  infection  or  purely  as  parasites. 

We  shall  confine  the  subject  to  streptococcus,  gono- 
coccus and  tuberculous  joint  infections  because  of  the 
usual  focal  origin.  The  deformities  which  occur  in 
chronic  arthritis  due  to  the  streptococcus  and  to  the 
gonococcus  do  not  differ  essentially  because  the  morbid 
anatomical  changes  which  are  produced  in  the  chronic 
type  of  infection  due  to  the  streptococcus  and  to  the 
gonococcus  are  essentially  the  same. 

In  both  instances  the  mode  of  infection  is  hemato- 
genous and  from  a  focal  infection.  In  both  the  obstruc- 
tion due  to  endothelial  proliferation  or  embolism  in  the 
small  arteries  due  to  the  hematogenous  mode  of  infec- 

107 


108  FOCAL  INFECTION 

tion  is  practically  the  same.  In  both  types  of  chronic 
infection  the  virulence  of  the  invading  organisms  is 
not  high.  Consequently  the  tissue  reactions  excited  by 
the  organisms  is  much  less  than  in  the  more  virulent 
type  of  streptococcus  and  gonococcus.  Consequently 
instead  of  the  production  of  a  positive  chemotaxis  with 
purulent  exudates  at  the  point  of  infection  as  with  local 
infections  due  to  the  streptococcus  pyogenes  and  viru- 
lent types  of  gonococcus,  there  is  in  these  chronic  con- 
ditions a  tendency  to  nbrinoplastic  exudate  and  an 
attempt  to  wall  off  an  area  of  infection.  The  variation 
in  the  virulency  of  the  organisms  which  produce  the 
chronic  types  may  result  in  serofibrinous  exudates  in 
joints  and  tendon  sheaths  and  to  small  hemorrhages  in 
subserous  tissues  and  in  muscles.  The  low  virulency 
of  the  organism,  the  embolic  mode  of  infection  of  the 
tissues,  the  resulting  tissue  reaction,  all  tend  to  lessen 
the  blood  supply  of  the  infected  tissues  through  the 
partial  obliteration  and  destruction  of  small  blood  ves- 
sels. In  consequence  there  is  a  lessened  blood  supply 
and  oxygenation  of  the  tissues  which  results  in  marked 
malnutrition.  Malnutrition  leads  to  secondary  meta- 
bolic changes  resulting  in  either  hyperplastic  or  atrophic 
changes  in  all  joint  structures,  tendons  and  muscles. 
These  changes  have  been  well  described  by  Nichols  and 
Richardson  (41)  as  both  proliferative  or  hypertrophic 
and  degenerative  or  atrophic  arthritis.  Because  of 
these  morbid  changes,  deformities  result  from  muscular 
contraction  and  from  the  changes  which  occur  in  the 
bones,  cartilage  and  other  structures  entering  into  the 
joints. 


CHRONIC  DISEASES  109 

Present  knowledge  is  in  accord  with  Nichols  and  Rich- 
ardson in  the  statement  they  make  that  morbid  changes 
both  proliferative  and  degenerative  of  joint  tissue  can- 
not be  differentiated  etiologically. 

If  one  considers  that  the  infection  of  joint  tissue  is 
hematogenous  and  that  a  sufficient  dose  of  infectious 
organisms  in  the  blood  stream  may  reach  the  peri-artic- 
ular tissue  or  deeper  tissue  of  the  joint — that  is,  the  end 
arteries  in  the  subcapsular  tissues — or  through  the 
nutrient  arteries  and  involve  the  medulla  of  the 
epiphysis,  one  can  harmonize  the  morbid  anatomical 
changes  which  have  been  so  clearly  described  by  Nichols 
and  Richardson. 

The  reaction  set  up  in  the  tissues  of  the  external  joint 
structures  in  the  subcapsular  region  and  in  the  medulla 
of  the  bone  will  depend  in  all  probability  upon  the 
virulence  of  the  infectious  microorganisms  and  upon 
the  resistance  of  the  general  body  structures  and  of  the 
joint  tissues.  They  may  be  either  proliferative  with 
virulent  bacteria,  especially  in  young  or  normal  indi- 
viduals, and  necessarily  the  reaction  will  be  less,  or  more 
degenerative  in  kind  in  the  joint  tissues  of  individuals, 
which  are  poor  because  of  age,  trauma  and  other  con- 
ditions which  lessen  the  vitality  of  tissue. 

Continued  doses  of  infection  from  the  focus  would 
necessarily  add  to  the  changes  described  in  the  joint 
tissue.  The  repeated  hematogenous  infection  destroys 
more  blood  vessels,  again  and  again  traumatizes  the 
infected  tissue  and  continuously  lessens  the  oxygen  sup- 
ply- 

We  now  know  that  in  chronic  arthritis  infectious 


110  FOCAL  INFECTION 

organisms,  whether  streptococci  or  gonococci,  have  a 
relatively  low  virulence.  Of  course  the  degree  of  viru- 
lence varies  and  consequently  the  proliferative  and  de- 
generative changes  especially  vary  in  different  indi- 
viduals. 

With  continued  infection  of  the  tissues  malnutrition 
necessarily  increases,  for  the  reasons  named,  and  this 
necessarily  leads  to  retrograde  metabolism. 

Whether  the  retrograde  metabolism  is  due  solely  to 
the  malnutritions  or  whether  it  is  also  due  in  part  to 
irritants  in  the  tissues  of  bacterial  or  biochemic  origin, 
does  not  in  any  way  alter  the  principles  outlined.  There- 
fore, the  proper  understanding  of  chronic  infectious 
arthritis  involves  an  understanding  of  the  following 
principles : 

(1)  The  infection  of  the  joints,  muscles  and  other 
involved  tissues  with  pathogenic  organisms  which  usu- 
ally are  members  of  the  streptococcus  group  and  the 
gonococcus  which  are  of  relatively  low  virulence ;  ( 2 )  a 
hematogenous  infection  with  embolism  with  resulting 
injury  of  blood  vessels  and  small  hemorrhages  into  the 
infected  tissues;  (3)  lessened  blood  supply  and  oxy- 
genation and  consequent  relative  starvation  of  the  in- 
fected tissues  and  dependent  upon  the  malnutrition, 
favorable  conditions  for  the  continued  life  and  multipli- 
cation of  the  infectious  organisms,  and  finally  (4)  retro- 
grade metabolism  due  to  the  malnutrition. 

In  the  chronic  infections  due  to  the  streptococcus, 
chronic  arthritis  may  occur  alone  or  associated  with 
chronic  myositis  and  chronic  myositis  may  also  occur 
alone  involving  single  or  groups  of  muscles.    In  chronic 


CHRONIC  DISEASES  111 

gonococcus  arthritis  the  muscles  are  rarely,  if  ever,  in- 
volved. Tenovaginitis  is,  however,  more  apt  to  occur 
than  in  chronic  streptococcus  infection. 

Various  anatomical  types  of  chronic  infectious  arthri- 
tis may  occur,  which  doubtless  depends  upon  the  de- 
gree of  bacteriemia,  the  degree  of  virulence  of  the  in- 
fectious organisms,  the  resistance  of  the  tissues  and  the 
fact  that  the  mode  of  infection  is  hematogenous.  Con- 
sequently we  may  have  a  peri-arthritis,  a  synovitis,  an 
osteo-arthritis  or  a  panarthritis.  Any  or  all  of  these 
types  may  exist  in  the  same  individual.  The  primary  in- 
fection may  be  severe  enough  to  simulate  acute  rheu- 
matic fever  or  mild  rheumatic  fever.  Usually  the  dis- 
ease begins  insidiously,  but  there  may  be  in  many  pa- 
tients periods  of  increase  in  temperature  usually  of  a 
febrile  type.  There  is  always  a  great  deal  of  soreness 
of  the  infected  tissues  which  is  aggravated  by  anything 
which  disturbs  the  general  or  local  circulation,  as  chilling 
the  body,  fatigue  and  general  nervous  irritability.  Be- 
cause of  the  varying  degrees  of  activity  of  the  focus 
there  may  be  reinfection  from  time  to  time  of  the  tis- 
sues, joints,  muscles,  etc.,  with  consequent  aggravation 
of  the  symptoms.  Usually  there  is  but  little  pain  ex- 
cepting with  exercise  of  the  involved  organs.  Chronic 
gonorrheal  arthritis  is  more  apt  to  involve  the  interver- 
tebral joints  and  ligaments,  the  sacroiliac,  sternoclavic- 
ular and  temporomaxillary  joints  than  the  strepto- 
coccus, but  inasmuch  as  the  streptococcus  may  also  infect 
the  four  named  joints,  involvement  of  them  does  not 
necessarily  indicate  a  gonococcus  infection.  Chronic 
infectious  myositis  which  may  occur  as  a  part  of  the 


112  FOCAL  INFECTION 

chronic  streptococcus  arthritis  or  alone,  is  associated 
with  shortening  of  the  muscle  bundles  due  to  the  embolic 
infection  with  subsequent  hemorrhage  and  connective 
tissue  proliferation.  At  the  time  of  infection  there  is 
usually  tenderness  and  pain  when  an  attempt  is  made 
to  contract  the  muscles.  When  at  rest  there  is  usually 
no  discomfort.  There  is  apparently  an  elective  affinity 
of  the  infectious  organism  for  certain  muscles,  notably 
the  masseters,  the  biceps  humeri,  the  hamstrings,  the 
anterior  tibial  and  erector  spinae  groups.  Other  muscles 
are  sometimes  involved  and  in  some  instances  practi- 
cally all  skeletal  muscles  are  included  in  the  infection. 

In  all  of  these  chronic  types  of  arthritis  and  myositis 
there  may  be  general  debility  with  anemia,  emaciation 
and  nervous  irritability  due  to  the  long  continued  infec- 
tion. Often  these  general  conditions  are  aggravated  by 
methods  of  treatment,  in  starvation  diets  and  purges 
which  weaken  the  patient  and  by  the  overuse  of  drugs. 
In  recent  years  the  irrational  use  of  vaccines  and  of  toxic 
extracts  of  bacteria  has  added  to  the  miserable  condi- 
tion of  the  patients. 

These  general  weakening  influences  add  to  the  con- 
ditions which  promote  retrograde  metabolism  in  the  in- 
fected tissues,  so  that  in  the  patients  who  present  the 
worst  type  of  the  condition  there  is  a  tendency  to  such 
a  degree  of  retrograde  metabolism  that  the  connective 
tissue  group  comprising  aponeurosis,  tendons  and  carti- 
lage is  changed  into  bone. 

Chronic  tuberculous  arthritis  is  always  associated  with 
focal  or  with  general  tuberculosis.  It  practically  always 
occurs  as  an  osteomyelitis  usually  involving  the  epiphy- 


CHRONIC  DISEASES  113 

sis.  The  evolution  of  the  tuberculous  process  in  the 
epiphysis  leads  to  infection  of  the  joint  with  its  char- 
acteristic morbid  anatomy.  Tuberculous  tenovaginitis 
is  usually  a  secondary  infection  from  the  periarticular 
tissues,  but  may  occur  alone. 

Spondylitis  due  to  the  typhoid  bacillus  probably 
causes  the  same  anatomical  type  as  the  gonococcus  and 
streptococcus. 

Infectious  neuritis  or  perineuritis  due  to  a  focus  of 
infection  may  occur  alone  or  as  a  part  of  chronic  ar- 
thritis and  myositis  or  with  myositis  without  arthritis. 
Usually  the  condition  is  a  perineuritis.  The  nerves  most 
often  involved  are  branches  of  the  brachial  plexus  and 
the  sciatic  trunks.  Focal  infection  about  the  teeth,  ton- 
sils and  sinuses  is  a  frequent  cause  of  neuritis.  The 
gonococcus  may  be  the  cause  of  neuritis  or  perineuritis. 

CHRONIC  INFECTIOUS  NEPHRITIS 

Chronic  infectious  nephritis  due  to  focal  infection  is 
very  common.  Probably  it  has  first  existed  as  a  sub- 
acute infectious  nephritis  and  not  infrequently  occurs  as 
a  hematogenous  infection  of  the  kidney  from  some  focus 
resulting  in  anatomical  changes  of  various  degrees. 
Chronic  infectious  nephritis,  like  the  subacute  and  acute 
types,  is  usually  due  to  strains  of  the  streptococcus 
which  have  a  specific  elective  affinity  for  the  kidney. 
This  specific  affinity  may  be  attained  in  the  focus  of 
infection.  If  the  bacteriemia  due  to  focal  infection  is 
severe,  undoubtedly  nephritis  either  acute  or  chronic 
may  result  from  bacteria  which  have  only  general  path- 
ologic virulence.    LeCount  and  Jackson  (35)  state  that 


114 


FOCAL  INFECTION 


the  most  important  result  of  their  work  was  the  experi- 
mental production  of  alterations,  essentially  subacute 
and  quite  like  the  acute  interstitial  nephritis  in  human 
kidneys,  caused  by  the  acute  infectious  diseases,  com- 


Fig.  61. — A  Typical  Subacute  Focal  Lesion  in  the  Cortex.    X  200  (after 
LeCount   and  Jackson,  Jour.   Inf.   Dis.). 

plicated  by  or  due  to  streptococcus  infection.  Of  the 
rabbits  inoculated,  eight,  or  25  per  cent,  of  the  thirty- 
three  which  died  or  were  killed  within  the  first  two 
weeks,  showed  chronic  changes  in  the  kidneys,  while  fif- 
teen, or  62.  5  per  cent.,  of  twenty-four  rabbits  which  lived 


CHRONIC  DISEASES  115 

from  fifteen  to  one  hundred  and  eighty-six  days,  showed 
chronic  kidney  changes.  They  conclude,  therefore,  that 
chronic  lesions  of  the  kidney  of  a  part  of  the  inoculated 


Fig.  62. — An  Interlobular  Vein  Surrounded  by  Lymphocytes  and 
Plasma  Cells.  From  the  kidney  of  rabbit  dying  42  days  after  inocu- 
lation.    X  35  (after  LeCount  and  Jackson,  Jour.  Inf.  Dis.). 

rabbits  resulted  from  the  subacute  nephritis  caused  by 
the  streptococci  intravenously  injected. 

Ophiils  (55)  concludes  that  chronic  nephritis  is 
usually  of  infectious  origin.  Klotz  (54)  states  that  a 
form  of  acute  interstitial  nephritis  induced  in  animals  by 


116  FOCAL  INFECTION 

the  inoculation  with  strains  of  streptococci  subsequently 
gives  rise  to  a  renal  sclerosis  of  the  type  known  as  chronic 
interstitial  nephritis.  He  believes  that  a  similar  process 
is  common  in  man. 

In  an  article  on  the  relation  of  focal  infection  to  ne- 
phritis, we  gave  the  clinical  history  of  a  young  woman 
who  suffered  with  hemorrhagic  nephritis  apparently  due 
to  badly  infected  tonsils.  After  enucleation  of  the  ton- 
sils there  was  great  improvement  of  the  renal  condition 
and  a  restoration  to  apparent  health.  Occasionally, 
slight  albuminuria  with  the  presence  of  hyalogranular 
casts  occurred.  After  one  year  evidences  of  chronic  in- 
terstitial nephritis  became  constant  and  three  years  fol- 
lowing the  removal  of  the  tonsils  and  the  greatly  im- 
proved condition,  the  patient  died  of  renal  intoxication 
associated  with  a  high  degree  of  hypertension. 

Every  clinician  of  experience  has  observed  patients 
over  long  periods  of  time  who  have  presented  primarily 
evidences  of  acute  or  subacute  nephritis  of  infectious 
origin  and  who  have  finally  succumbed  to  chronic 
nephritis.  That  a  focal  infection  may  be  the 
source  of  the  kidney  lesions  and  may  lead  to  a 
chronic  irreparable  renal  disease  must  be  emphasized. 
Early  removal  of  the  etiologic  focus  may  prevent  fur- 
ther anatomical  insult  of  the  kidneys  and  preserve  renal 
function  and  life. 

CHRONIC  CHOLECYSTITIS 

Chronic  cholecystitis  with  or  without  gall-stones  is 
the  result  of  acute  infection  as  a  rule.  As  we  have  seen, 
this  may  be  due  to  hematogenous  streptococcus  infec- 


CHRONIC  DISEASES  117 

tion.  The  streptococci,  which  lodge  in  the  small  area 
of  the  fundus  of  the  gall-bladder  at  the  terminus  of  a 
blood  vesseL  may  cause  hemorrhage  and  exciting  tissue 


• 

m  .  ■ 

9 

>*^Bfll 

k^H 

f' •'•-','-(.  J';*,,- ;*>»^B 

^K  ■            fcfl 

W&ywmm 

k  V c  v'^i 

KP-;  '^^F  A 

\  (J 

Fig.  63. — Cholecystitis  and  Cholelithiasis  in-  Dog  Ten  Days  After  In- 
travenous Injection  of  Streptococcus  from  Center  of  Gall-Stone 
from  Human  Gall-Bladder.  Note  the  black  stones  imbedded  in  the 
edematous  mucous   membrane. 

reaction  which  weakens  the  gall-bladder  wall  and  may- 
rupture  into  the  cyst.  If  the  infectious  organism  is  of 
high  virulency,  acute  purulent  cholecystitis  may  occur 


118 


FOCAL  INFECTION 


or  with  a  less  virulent  type  the  infection  will  be  much 
less  in  degree.  If  unoperated  at  the  time  of  the  acute 
or  subacute  attack,  gall-stones  may  form  in  the  chroni- 
cally infected  gall-bladder.  As  long  as  the  focal  site 
exists  reinfection  may  lead  to  subsequent  acute  or  sub- 
acute attacks  of  cholecystitis. 

As  shown  by  Rosenow  (8)  the  strain  of  strepto- 
coccus, which  seems  to  acquire  an  affinity  for  the  tissue 
of  the  gall-bladder,  has  a  coincident  affinity  for  muscles 
particularly  of  the  myocardium,  and  in  confirmation 
clinicians  have  noted  evidences  of  myocardial  weakness 
in  patients  who  suffer  from  chronic  cholecystitis. 


CHRONIC  PEPTIC  ULCER 


Chronic  peptic  ulcers  of  the  stomach  and  duodenum 
are  doubtless  the  sequence  of  acute  ulceration  and  we 
have  already  noted  the  mode  of  infection  in  acute  ulcer 


Fig.  64. — Streptococci  and  Leukocytic  Infiltration  in  Peritoneal  Coat 
in  Perforating  Ulcer  of  the  Stomach  of  Man. 


Fig.  65. — Streptococci  in  Peritoneal  Coat  of  Ulcer  of  Stomach  in 
Rabbit  5  Days  After  Intravenous  Injection  of  Streptococci  from 
Perforating   Ulcer  of  Stomach  in  Man   Shown  in  Fig.  64. 


Fig.   66. — Streptococci  and  Leukocytic  Infiltration   in   Chronic   Ulcer 
of  Man  with  Acute  Exacerbation  Shortly  Before  Operation. 


119 


Fig.  67.  Chronic  Ulcer  of  Duodenum  of  Dog  13  Weeks  After  Single 
Intravenous  Injection  of  Streptococcus  from  Ulcer  of  the  Duo- 
denum of  Man. 


Fig.  68. — Chronic  Ulcer  of  Duodenum  of  Dog  13  Weeks  After  a  Single 
Intravenous  Injection  of  Streptococcus  from  Human  Ulcer.  Note 
the  displacement  of  muscular  layer  (a)  by  connective  tissue  and  the 
thickened  peritoneal  coat   (b). 


120 


CHRONIC  DISEASES  121 

and  the  immediate  morbid  tissue  changes  which  occur. 
In  the  hematogenous  embolic  infection  of  the  stom- 
ach with  a  strain  of  the  streptococcus  which  has  an 
elective  affinity  for  the  stomach  wall,  a  local  sub- 
mucous hemorrhage  occurs.  In  consequence  of  the 
hemorrhage  and  infection,  anemic  necrosis  results  with 
consequent  lessened  resistance  and  the  necrosed  tissues 
of  this  small  area  are  digested  by  the  gastric  juice.  The 
continued  infection  of  the  tissues  around  the  acute  ulcer 
prevents  the  healing  of  the  mucous  membrane  of  the 
stomach  in  all  probability,  for  it  is  well  known  that 
uninfected  wounds  of  the  stomach  readily  heal.  The 
continued  action  of  the  gastric  juice  upon  the  ulcer  base 
results  in  the  characteristic  anatomical  picture  of  chronic 
peptic  ulcer. 

CHRONIC  INFECTIOUS  ENDOCARDITIS 

In  1903  Schottmiiller  (10)  reported  the  isolation  of 
a  green-forming  streptococcus  in  blood  agar  plates  from 
the  blood  of  patients  suffering  from  endocarditis.  This 
report  was  made  in  connection  with  the  investigation 
which  Schottmiiller  was  at  that  time  making  of  the 
growth  characteristics  of  streptococci  upon  blood  agar. 
He  called  this  green-producing  microorganism  strepto- 
coccus viridans.  Its  low  virluency  led  also  to  the  name, 
streptococcus  mitior. 

The  character  of  the  endocarditis  in  which  the  strepto- 
coccus viridans  seemed  to  be  the  infectious  agent  has 
proved  to  be  one  of  a  paradoxical  nature  in  the  sense 
that  the  clinical  course,  in  the  early  stages,  is  frequently 
very  mild  and  the  patient  is  able  often  to  be  up  and 


122  FOCAL  INFECTION 

about,  even  attending  to  ordinary  affairs  of  life,  but  it  is 
progressive  and  in  a  few  weeks  or  months,  sometimes  as 
late  as  a  year  and  a  half,  the  patient  usually  succumbs 
to  the  disease. 

It  is,  therefore,  a  malignant  type  of  endocarditis  al- 
though usually  chronic  in  its  clinical  course.  As  I  have 
before  stated  the  streptococcus  viridans  endocarditis 
may  sometimes  be  very  acute  and  associated  with  a  septic 
type  of  temperature  with  a  very  high  maximum  and 
low  minimum  temperature,  and  may  run  its  entire  clin- 
ical course  within  two  or  three  weeks.  During  the  last 
few  years  since  routine  blood  cultures  have  been  made, 
the  frequent  incidence  of  this  disease  has  become  noted. 
Osier  (17),Horder  (18),Libman  (20),  Lenhartz  (22) 
and  others  have  reported  a  series  of  patients  suffering 
from  what  they  have  termed  chronic  infectious  endo- 
carditis, infective  endocarditis,  subacute  infective  endo- 
carditis, subacute  bacterial  endocarditis  and  the  report 
which  Rosenow  and  Billings  made  was  under  the  title 
of  "chronic  pneumococcus  endocarditis." 

The  characteristics  of  this  type  of  malignant  endo- 
carditis are  usually  a  mild  clinical  course  in  which  the 
patient  may  complain  of  lessened  strength  and  endur- 
ance; usually  a  poor  appetite;  more  or  less  dyspnoea 
of  exertion;  slight  to  severe  chills  and  fever  in  periods 
often  mistaken  for  malaria;  cough,  in  some  cases  with 
more  or  less  expectoration,  often  with  a  septic  type  of 
fever  mistaken  for  tuberculosis,  and  in  severe  grades 
sometimes  treated  for  mild  typhoid  fever.  The  major- 
ity of  these  patients  have  suffered  at  some  time  from 
rheumatism  and  endocarditis  or  from  endocarditis  alone 


CHRONIC  DISEASES  123 

and  upon  examination  it  is  usual  to  find  the  evidences 
of  old  valvular  disease  with  varying  conditions  as  to  the 
heart  muscle.  Those  patients  who  have  not  previously 
suffered  from  endocarditis  may  present  no  heart  mur- 
murs or  other  evidence  of  heart  involvement.  While 
in  bed  the  temperature  is  usually  a  mildly  febrile  one 
of  septic  type  and  there  may  be  rigors  amounting  at 
times  to  severe  chills.  Sooner  or  later  with  involvement 
of  the  left  heart  there  are  evidences  of  embolism  in 
petechia  of  the  skin  and  elsewhere.  Frequently  there  are 
infarcts  of  the  spleen  manifested  by  enlargement  and 
tenderness  of  that  organ.  Infarcts  of  the  kidney  mani- 
fested by  hematuria  usually  microscopic  (See  Baehr 
(23)  and  Lohlein  (24) ) ,  embolism  of  brain  with  varying 
degrees  of  sensory  or  motor  disturbance  and  in  some 
patients  embolism  of  sufficient  size  of  the  arteries  of 
the  extremities  to  obliterate  the  pulse  below  the  site  of 
the  embolus  and  to  cause  gangrene  of  the  extremities. 
Mycotic  aneurism  may  occur  usually  situated  in  the 
smaller  arteries.  Death  supervenes  with  severe  embol- 
ism of  the  brain  or  from  exhaustion  with  mixed  infec- 
tion. The  duration  may  be  from  two  to  three  weeks  in 
the  really  acute  types  of  the  disease  and  may  last  for 
eighteen  or  more  months. 

The  streptococcus  viridans  may  be  isolated  from  the 
blood  and  is  characterized  by  the  fact  that  in  culture 
media  it  soon  loses  its  affinity  for  the  heart  and  may  be 
converted,  as  shown  in  the  immunological  studies  of 
Rosenow  (8),  into  any  of  the  other  types  of  the  mem- 
bers of  the  streptococcus-pneumococcus  group. 

The  lesion  of  the  heart  in  streptococcus  viridans  en- 


124  FOCAL  INFECTION 

docarditis  is .  characterized  by  the  growth  of  massive 
vegetations  upon  the  valves  and  upon  the  mural  endo- 
cardium. (See  Figs.  9  and  10.)  It  is  not  usually 
attended  with  ulcerations,  but  there  is  an  enormous 
deposit  of  thrombus  in  the  vegetations  which  serves  as 
a  rich  culture  medium  for  the  invading  organism  and 
also  because  of  the  size  and  friability  of  the  vegetations 
and  the  thrombus  formation  is  a  ready  source  for  the  dis- 
semination of  emboli  of  all  sizes  through  the  systemic 
vessels. 

It  is  a  non-pus-forming  organism  and  consequently 
suppuration  does  not  follow  in  the  tissues  involved  in 
the  embolism.  In  rare  instances  the  mycotic  aneurism 
may  break  into  the  surrounding  tissues  and  in  two  pa- 
tients under  my  observation  abscesses  formed  and  a 
pneumococcus  was  obtained  in  pure  culture  therefrom, 
while  in  the  blood  stream  was  found  the  streptococcus 
viridans  in  pure  culture. 

The  streptococcus  viridans  endocarditis  is  usually 
fatal.  Streptococcus  viridans  bacteriemia  unassociated 
with  endocarditis,  although  there  may  be  an  endocardial 
murmur  present,  is  not  necessarily  fatal.  The  reports 
of  recoveries  of  streptococcus  viridans  endocarditis  may 
be  of  those  patients  who  have  streptococcus  viridans  bac- 
teriemia without  a  real  endocarditis.  Libman  has  re- 
ported recoveries,  and  in  a  series  reported  by  Horder 
the  mortality  was  not  absolute.  In  my  own  experience 
only  three  patients  out  of  more  than  one  hundred  who 
have  had  a  streptococcus  viridans  bacteriemia  have  recov- 
ered from  that  condition.  In  one  of  these  there  was  no 
recognizable  heart  murmur  and  the  condition  was  asso- 


CHRONIC  DISEASES  125 

ciated  with  streptococcus  viridans  infarct  of  the  right 
lung  with  suppuration,  evacuation  of  abscess  and  recov^ 
ery.  In  another,  a  boy  of  sixteen,  with  a  systolic  mitral 
murmur  and  moderate  septic  fever,  the  bacteria  finally 
disappeared  from  the  blood  and  recovery  ensued  with 
moderate  mitral  insufficiency  fully  compensated.  In  a 
third  patient,  a  Jewess,  with  mitral  stenosis  and  mod- 
erate septic  fever  of  long  duration  mistaken  before  en- 
tering the  Presbyterian  Hospital  for  tuberculosis  of 
the  lung,  the  bacteriemia  disappeared  and  five  years  later 
the  patient  was  entirely  well  except  for  the  mitral  sten- 
osis, fully  compensated. 

Even  with  evidences  of  endocarditis  in  the  last  two 
patients  described,  it  was  not  proved  that  there  was  an 
endocarditis  of  recent  origin. 

The  character  of  the  changes  in  the  myocardium  and 
valves  is  so  serious  in  this  disease,  very  much  like  that  of 
the  acute  malignant  endocarditis  due  to  the  pneumo- 
coccus,  that  one  can  appreciate  the  fatal  nature  of  the 
condition. 

That  healing  may  occur  though  rarely  cannot  be 
doubted  when  one  examines  the  heart  in  an  accidental 
death  with  coroner's  inquest  where  the  enormous  vegeta- 
tions can  still  be  recognized  but  so  infiltrated  with  cal- 
cium salts  that  a  practical  cure  has  resulted.  This  condi- 
tion has  been  noted  as  I  have  stated  previously  in  the  ob- 
servation of  LeCount. 

The  focus  of  infection  which  undoubtedly  causes  the 
streptococcus  viridans  bacteriemia  and  chronic  malig- 
nant endocarditis  is  often  alveolar  abscess.  Of  this  we 
have  had  numerous  clinical  examples.     Coincident  cul- 


126  FOCAL  INFECTION 

tures  from  the  alveolar  abscess  and  from  the  blood 
have  yielded  strains  of  streptococcus  viridans.  When 
these  nascent  cultures  were  intravenously  injected  into 
animals,  typical  endocardial  lesions  resulted.  Doubt- 
less a  focus  containing  this  streptococcus  may  be  lo- 
cated in  the  tonsil  or  nasal  sinus  or  elsewhere  which 
may  be  the  source  of  the  cardiac  infection. 


LECTURE  V 

TREATMENT 
FOCAL  INFECTION 

Prevention  of  focal  infection  is  an  important  prin- 
ciple in  the  consideration  of  the  treatment  of  the  etio- 
logic  factor  and  the  related  systemic  infections. 

We  may  not  hope  so  to  modify  the  actions  of  indi- 
viduals or  of  society  that  communicable  diseases  will  dis- 
appear or  that  susceptibility  to  infection  will  be  over- 
come in  the  evolution  of  a  mentally  and  physically  bet- 
ter developed  race,  for  we  cannot  wholly  prevent  or 
abolish  the  marriage  or  procreation  of  the  unfit;  vice; 
alcoholic  and  drug  addictions ;  poverty,  unhealthf ul 
domiciliary  and  occupational  environment;  the  use  of 
contaminated  food  and  drink ;  community  uncleanliness, 
and  other  causes  of  mental  and  physical  debility  which 
directly  diminish  the  natural  body  defenses. 

The  control  of  these  debility-producing  factors  is  a 
function  of  national,  state  and  municipal  public  health 
bodies.  Politics,  greed  for  wealth  and  ignorance  are 
influences  which  prevent  the  administration  of  well-es- 
tablished laws  which,  if  properly  enforced,  would  do 
much  to  abolish  unhealthful  conditions  and  disease. 

As  far  as  possible,  as  individuals  and  collectively,  phy- 
sicians should  exert  an  influence  to  promote  cleanliness 

of  mind  and  body  and  thus  lessen  the  incidence  of  focal 

127 


128  FOCAL  INFECTION 

and  systemic  infection.  The  encouragement  of  per- 
sonal cleanliness  and  especially  the  care  of  the  skin  and 
its  appendages,  and  of  the  mouth  and  throat  should  be 
a  duty  of  the  family  physician.  The  necessity  of  cleans- 
ing the  mouth,  teeth  and  throat  of  all  particles  of  food 
after  eating  should  be  taught  as  a  prevention  of  local 
infection,  decay  of  teeth  and  of  general  disease.  When 
other  measures  fail  the  removal  of  the  persistent  over- 
growth of  lymphoid  tissue,  a  good  culture  medium  for 
bacteria,  of  the  nasopharynx  and  throat  should  be  ad- 
vised. Chronically  enlarged  pharyngeal  tonsils,  which 
obstruct  the  upper  respiratory  tract  and  prevent  proper 
ventilation  and  drainage,  invite  local  infection  of  the 
mucous  tracts  of  the  head  and  should  be  totally  re- 
moved. 

The  foregoing  statements  are  applicable  chiefly  in 
childhood,  for  children  are  especially  susceptible  to  in- 
fection of  the  tissues  of  the  mouth,  throat,  nose,  acces- 
sory sinuses,  middle  ear  and  mastoid  cells.  We  know 
that  freedom  from  streptococcus  infection  of  the  mucous 
membrane  and  lymphoid  tissues  of  the  head  would  very 
much  lessen  the  incidence  of  rheumatism,  chorea  and 
endocarditis  in  children  and  also  in  adults.  We  may  not 
as  confidently  expect  to  prevent  acute  appendicitis,  pep- 
tic ulcer,  cholecystitis  and  nephritis  by  these  measures; 
still,  the  evidence  of  the  etiologic  relations  of  these  dan- 
gerous local  infections  to  focal  nose,  mouth  and  throat 
infection  is  so  strong  that  the  correction  of  these  confined 
infections  is  rationally  indicated.  I  do  not  wish  to  seem 
to  be  an  advocate  of  unnecessary  operations,  for  many 
operations  of  all  kinds  are  irrationally  performed,  in- 


TREATMENT  129 

eluding  the  removal  of  overgrowth  of  the  tonsils  and 
other  lymphoid  and  mucous  tissues  of  the  nose  and 
throat.  These  conditions  of  the  nose  and  throat  may 
disappear  with  a  proper  hygienic  management.  I  believe 
that  tonsillectomy  is  often  needlessly  performed  for  the 
relief  of  a  systemic  infection,  when  the  real  focal  cause 
is  situated  elsewhere.  Doubtless  the  normal  faucial  ton- 
sillar tissue  has  a  beneficent  function  and  uninfected, 
should  not  be  molested.  But  too  often  the  tonsillar 
tissue  in  children  and  also  in  some  adults  is  a  culture 
medium  of  pathogenic  bacteria  and  as  such  is  a  constant 
source  of  danger  as  a  portal  of  entry  of  infectious  bac- 
teria through  the  lymph  and  blood  streams  to  the  tissues 
of  the  body.  Infected  tonsils  cannot  be  successfully 
sterilized  by  any  known  method  of  treatment  and  entire 
removal  is  the  only  safe  procedure.  If  necessary  a  prop- 
erly directed  surgical  treatment  of  the  easily  recog- 
nized morbid  anatomical  condition  of  the  nasopharynx 
and  nares  will  establish  normal  ventilation  and  drainage 
and  lessen  the  incidence  of  middle  ear,  mastoid  and 
accessory  sinus  disease  with  the  resulting  possible  sys- 
temic involvement  from  these  sites  of  focal  infection. 
Until  recently  the  importance  of  pyorrhea  dentalis  and 
alveolar  abscess  as  an  etiologic  factor  in  systemic  infec- 
tion has  not  been  recognized.  Clinical  and  laboratory 
observation  and  research  have  definitely  settled  the 
question.  As  has  been  stated  in  the  first  lecture,  the 
members  of  the  streptococcus  group,  but  occasionally 
other  bacteria,  are  the  pathogenic  agents  of  pyorrhea 
which  cause  systemic  infection.  The  endameba  buccalis 
may  have  an  etiologic  relation  to  the  pyorrhea  of  the 


130  FOCAL  INFECTION 

teeth  and  alveoli,  may  intensify  the  destructive  local  dis- 
ease and  may  be  the  agents  of  communicating  the  dis- 
ease to  others  by  direct  personal  contact  or  through  fo- 
mites.  The  existence  of  focal  infection  of  the  jaws  in  the 
form  of  chronic  alveolar  abscess,  without  the  manifesta- 
tion of  much  discomfort,  is  remarkable.  The  condition 
is  often  not  discoverable  by  inspection  and  escapes  the 
attention  of  the  physician  and  the  dentist.  It  is  only 
when  destructive  lesions  of  the  gum,  tooth  and  alveolus 
make  the  condition  visible  that  a  diagnosis  is  usually 
made.  Properly  made  Rontgen  ray  films  of  the  jaws 
will  enable  one  to  recognize  the  real  morbid  and  ana- 
tomical condition.  The  definite  recognition  of  the  con- 
dition and  the  character  of  the  mechanical  dentistry 
which  should  be  practiced  demands  the  use  of  Rontgen 
ray  films  of  the  jaws.  The  use  of  emetin  in  the  destruc- 
tion of  the  endameba  may  rid  the  mouth  temporarily  of 
an  etiologic  factor  of  pyorrhea,  but  the  drug  does  not 
remove  the  infectious  bacteria  in  the  focus,  nor  does  it 
restore  the  periosteum  of  the  root  of  the  tooth  without 
which  the  tooth  ceases  to  be  living  bone  and  as  a  foreign 
body  invites  added  and  continued  bacterial  infection. 

In  a  consideration  of  amebic  dysentery,  Phillips  (51) 
states  that  emetin  will,  kill  the  parasite  in  the  active 
stage,  while  the  drug  has  but  little  or  no  effect  on  the 
cysts.  He  suggests  the  hypodermic  use  of  emetin  in  ten- 
day  periods,  with  gradually  increasing  intervals,  until 
repeated  examinations  finally  fail  to  find  endamebas  in 
the  stool.  Inasmuch  as  emetin  destroys  endameba 
buccalis,  the  same  method  of  management  may  more 
certainly  rid  the  mouth  of  the  parasite. 


TREATMENT  131 

Dentists  everywhere  are  interested  in  the  better  man- 
agement and  correction  of  alveolar  infection.  We  must 
look  to  them  for  a  treatment  which  will  destroy  the 
focal  infection  of  the  jaws  and  safeguard  the  individual 
from  systemic  infection.  Deplorable  as  the  loss  of  teeth 
may  be,  that  misfortune  is  justified  if  it  is  necessary  to 
obliterate  the  infectious  focus  which  is  a  continued 
menace  to  the  general  health. 

Malnutrition  and  general  debility  due  to  chronic  dis- 
ease, old  age,  and  other  causes  may  lead  to  focal  infec- 
tion of  the  jaws.  Such  foci  of  infection  tend  to  add  in- 
fection to  already  infected  systemic  tissues.  These  in- 
fectious foci,  which  in  a  way  are  secondary  to  the  sys- 
temic disease  causing  the  general  debility,  are  just  as 
dangerous  as  primary  foci  and  should  be  removed. 

Persistent  lymph  node  infections  which  do  not  dis- 
appear with  hygienic  measures  instituted  to  improve  the 
defenses  of  the  body  should  be  surgically  removed  as  a 
matter  of  protection  against  the  further  dissemination 
of  tuberculosis  or  of  some  other  disease  from  the  specifi- 
cally infected  nodes. 

The  conditions  which  may  promote  infection  of  the 
gastro-intestinal  tract  are  usually  not  brought  to  the 
attention  of  the  physician  until  too  late  to  use  measures 
of  prevention.  Myriads  of  infectious  bacteria  are  swal- 
lowed in  infected  food,  especially  milk,  and  in  the 
muco  pus  of  the  nose,  throat  and  bronchi.  The  gastric 
juice  and  other  digestive  fluids  probably  destroy  most 
of  these  bacteria  in  robust  individuals.  The  surviving 
microorganisms  may  reach  the  tissues  of  the  bowel 
and     the     adjacent     lymph     nodes,     under     favor- 


132  FOCAL  INFECTION 

able  conditions  may  continue  to  have  or  may 
attain  pathogenic  virulence,  and  cause  local  or 
systemic  disease.  Habitual  constipation,  with  or 
without  congenital  or  acquired  anatomical  de- 
formities of  the  intestinal  tract,  may  lower  the  natural 
resistance  of  the  tissues  to  invasion  by  the  bacteria  of 
the  intestine.  Again  the  morbid  anatomical  conditions 
which  favor  intestinal  stasis  may  promote  increased 
general  virulence  or  elective  tissue  affinity  of  the  in- 
vading bacteria.  Rosenow  (8)  has  demonstrated  an 
acquired  virulence  and  also  an  elective  tissue  affinity 
for  the  appendix  of  a  strain  of  colon  bacilli  isolated  in 
cultures  from  the  exudate  and  tissues  in  patients  with 
appendicitis.  When  injected  intravenously  appendi- 
citis developed  in  the  inoculated  animals.  After  a  time 
the  general  virulence  and  specific  tissue  affinity  was  lost 
in  subcultures  of  this  strain.  Beaussenat  quoted  by 
Adrian  (28)  was  unable  to  produce  appendicitis  by 
the  intravenous  injection  of  ordinary  strains  of  colon 
bacilli  without  first  injuring  the  mucous  membrane  of 
the  organ. 

Infection  of  the  digestive  tract  may  be  prevented 
or  at  any  rate  its  incidence  may  be  diminished  very 
much  by  obliterating  the  sources  of  the  mucopus  in  the 
throat  and  nose,  which  at  the  same  time  removes  the 
foci  of  infection  of  the  head,  and  also  by  avoiding  in- 
fected food. 

Stasis  of  the  bowels,  whether  due  to  habitual  consti- 
pation or  to  congenital  or  acquired  anatomical  condi- 
tions, should  have  a  proper  medical  management  or,  if 
necessary,  surgical  treatment.     I  very  much  doubt  if 


TREATMENT  133 

the  removal  of  the  entire  colon  is  justifiable  for  ntestinal 
stasis  alone;  certainly  not  to  the  degree  practiced  by 
some  surgeons.  Chronic  appendicitis  with  lessened  tis- 
sue resistance  invites  acute  attacks,  disturbs  the  gastric- 
digestion  and  may  be  a  focus  of  systemic  infection.  The 
same  is  true  of  chronic  cholecystitis  and  especially  as 
the  experiments  of  Rosenow  (8)  seem  to  show  that  the 
streptococcus  strains,  which  acquire  an  elective  affinity 
for  the  gall-bladder,  have  also  an  affinity  for  muscular 
tissue,  especially  the  myocardium.  This  confirms  the 
clinical  observation  of  the  occurrence  of  cardiac  muscle 
disease  with  cholecystitis.  Therefore,  surgery  is  indi- 
cated in  appendicitis  and  cholecystitis  to  relieve  the  in- 
dividual of  a  local  menace  to  life,  of  reflex  dyspepsia 
and  quite  as  important  to  remove  etiologic  factors  of 
systemic  disease. 

The  morbid  conditions  of  the  rectum,  which  makes 
it  a  dangerous  source  of  lymphogenous  and  hematoge- 
nous infection  especially  of  colon  bacilli  and  strepto- 
cocci, should  receive  rational  surgical  treatment. 

The  focal  acute  and  chronic  infectious  diseases  of  the 
pelvic  organs  of  woman,  particularly  of  the  uterus  in 
the  puerperium  and  of  the  parametrium  and  fallopian 
tubes,  are  so  important  that  they  should  be  rationally 
managed  and  surgically  treated  when  necessary  to  safe- 
guard health  and  life. 

The  alleged  etiological  relation  of  chronic  streptococ- 
cus infection  to  cystic  degeneration  of  the  ovary  needs 
confirmatory  bacteriologic  research.  This  is  especially 
needed  if  the  supposed  infectious  cause  of  diseases  of  the 
ovary  is  accepted  as  an  additional  excuse  for  the  too 


134  FOCAL  INFECTION 

frequent  sacrifice  of  the  ovary  for  the  numerous  real 
and  fancied  ills  of  women. 

The  infectious  foci  of  the  male  pelvic  organs  requires 
a  management  and  surgical  treatment  which  will  re- 
move a  constant  source  of  systemic  diseases  and  in 
gonorrheal  infection  in  addition,  a  source  of  the  most 
frequent  cause  of  pelvic  disease  of  women,  many  of 
whom  are  morally  innocent  wives.  As  demonstrated 
by  Sugimura  (4)  and  Franke  (5),  lymphogenous  in- 
fection in  addition  to  other  sources  of  hematogenous 
infection  of  the  ureter,  kidney  pelvis  and  kidney,  from 
the  bladder,  indicates  additional  reasons  for  effective 
treatment  medical  or  surgical  to  overcome  acute  and 
chronic  cystitis.  So,  too,  may  rational  medical  or  surgi- 
cal treatment  of  pyogenic  and  tuberculous  kidney  and 
kidney  pelvis  infections  prevent  corresponding  infection 
of  the  ureter,  bladder,  other  pelvic  organs,  and  from  all 
of  these  sources  a  general  systemic  infection. 

Infected  wounds,  often  insignificant,  of  the  skin  and 
mucous  membranes  and  furuncles  and  purulent  infec- 
tion about  the  finger  and  toe  nails  should  receive  the 
management  which  is  indicated  by  the  rare,  yet  often 
serious,  systemic  infections  which  they  may  cause. 

TREATMENT  OF  RESULTING  ACUTE  AND  CHRONIC  SYSTEMIC 

DISEASES 

In  the  treatment  of  disease  it  is  an  axiom  to  remove 
the  cause  if  possible.  This  law  of  good  medical  practice 
is  applicable  in  diseases  due  to  focal  infection.  In  some 
acute  diseases  it  is  impossible  to  remove  the  focal  dis- 
ease, either  because  it  is  inaccessible  or  the  serious  con- 


TREATMENT  135 

dltion  of  the  patient  contraindicates  it.  In  bacteriemia 
due  to  puerperal  sepsis,  or  to  an  infectious  thrombo- 
phlebitis of  the  deep  veins,  surgery  cannot  be  utilized 
without  danger  of  death  from  shock  or  from  an  over- 
whelming degree  of  bacteriemia  by  a  physical  disturb- 
ance of  the  infected  thrombus  or  other  tissue  sources  of 
the  infection. 

In  acute  rheumatic  fever  associated  with  en- 
docarditis, pericarditis  or  a  pancarditis,  the  serious 
condition  of  the  patient  usually  contraindicates  tonsil- 
lectomy for  the  removal  of  the  most  general  etiologic 
focus.  Experience  teaches  that  removal  of  the  tonsils 
during  an  attack  of  acute  rheumatic  fever  usually  does 
not  modify  the  clinical  course.  It  is  the  better  practice 
to  remove  the  focal  cause,  wherever  it  may  be,  in  the  late 
convalescence. 

In  mild  rheumatic  fever  and  in  chronic  infectious 
forms  of  arthritis  the  focal  cause  should  be  removed 
early.  Even  in  these  mild  and  chronic  types  of  infec- 
tious arthritis  and  myositis  one  occasionally  witnesses 
serious  results.  A  girl  of  eighteen  who  had  suffered  for 
a  year  from  a  disabling  chronic  polyarthritis  and  myo- 
sitis, due  apparently  to  multiple  chronic  alveolar  ab- 
scesses, had  many  teeth  extracted  and  the  alveolar  ab- 
scesses curetted.  Streptococcus  bacteriemia  developed 
with  acute  hemorrhagic  myositis,  pleuritis,  pericarditis, 
myocarditis  with  submucous  and  subcutaneous  hemor- 
rhages and  death.  The  streptococci  isolated  from  the  al- 
veolar pus,  the  blood  and  after  death  from  the  muscles, 
when  injected  intravenously  into  animals  caused  rheu- 
matic arthritis,  myositis,  endocarditis  and  pericarditis. 


136  FOCAL  INFECTION 

A  girl  of  ten,  now  a  patient  in  the  Presbyterian  Hos- 
pital, suffered  from  a  mild  arthritis  and  myositis.  The 
family  physician  had  the  enlarged  and  apparently  in- 
fected tonsils  removed.  Immediately,  there  developed 
an  acute  general  myositis,  which  gradually  changed  to  a 
non-febrile  type  with  much  deformity  due  to  the  shorten- 
ing of  the  muscles.  Experience  of  this  kind  affords  proof 
of  the  focal  origin  of  certain  systemic  conditions  and 
that  the  operative  technic  of  removal  of  foci  of  infec- 
tions should  be  of  a  kind  which  will  not  overwhelmingly 
inoculate  the  patient.  In  acute  rheumatic  infections  the 
removal  of  the  original  focus,  usually  tonsillitis,  may 
not  prevent  future  attacks,  for  the  streptococcus  rheu- 
maticus  may  occur  in  other  focal  sites,  notably  in 
alveolar  abscess  and  maxillary  sinusitis.  The  prompt 
removal  of  every  recognizable  local  infection  of  the  head, 
in  people  who  suffer  from  repeated  attacks  of  acute 
rheumatism,  may  prevent  the  disease.  This  result  ex- 
perience of  recent  years  has  conclusively  proved.  What 
has  been  said  of  the  treatment  of  the  acute  rheumatic  in- 
fections is  also  true  of  chorea.  But  experience  has 
shown  that  arsenic  does  modify  the  cause  of  chorea. 
It  is  interesting  to  note,  in  this  connection,  that  arsenic 
has  also  a  striking  influence  on  the  clinical  course  of 
rheumatic  pericarditis  and  pleuritis.  I  have  used  caco- 
dylate  of  soda  as  a  relatively  non-toxic  form  of  arsenic 
in  the  treatment  of  chorea  and  of  serofibrinous  rheu- 
matic pericarditis  and  pleuritis.  From  five  to  fifteen 
grains  in  divided  doses,  each  twenty-four  hours,  injected 
deep  in  the  muscles,  has  a  remarkable  effect  within  two 
or  three  days.    The  uniformly  constant  result  suggests 


TREATMENT  137 

a  chemotherapeutic  result  similar  to  that  of  salvarsan 
for  spirochetes. 

Salicylic  acid  seems  to  have  a  specific  bactericidal 
effect  upon  the  streptococcus  rheumaticus  if  it  is  given 
in  sufficient  quantity  in  the  first  days.  Large  sterilizing 
doses  given  early  seem  necessary.  Perhaps  the  strepto- 
coccus becomes  immune  to  ineffectual  doses  of  the  drug, 
and  this  may  explain  the  lack  of  specific  effect  in  the 
prolonged  clinical  course.  It  is  of  interest  to  record 
the  apparent  good  effect  of  large  doses  of  salicylic  acid 
during  the  first  hours  of  acute  appendicitis,  which  as 
we  have  noted  may  be  caused  by  a  modified  strain  of 
the  streptococcus  rheumaticus. 

Acute  gonorrheal  arthritis  must  first  be  recognized 
by  the  pathognomonic  signs  sometimes  present,  purulent 
exudate  in  joints  and  tendon  sheaths,  the  gonococcus 
in  exudates  and  blood  and  the  recognition  of  a  focus 
in  the  genito-urinary  tract.  The  specific  von  Pirquet 
skin  and  the  complement  fixation  tests  are  not  always 
to  be  relied  upon  in  diagnosis  unless  suitably  controlled, 
according  to  Irons  (36),  Irons  and  Nicoll  (37).  The 
almost  uniform  benefit  of  the  early  removal  of  the  focal 
cause  is  notable  in  systemic  gonococcus  infection.  Even 
with  gonococcemia,  if  no  involvement  of  the  endocar- 
dium occurs  and  if  there  is  no  gonococcus  thrombo- 
phlebitis, the  removal  of  the  focus  is  often  followed  by 
recovery.  Purulent  exudates  must  be  surgically  treated. 

Malignant  endocarditis  of  all  types  is  usually  fatal 
because  the  invading  bacteria  find  lodgment  and  suit- 
able conditions  for  growth  and  multiplication  in  large 
vegetations  filled  with  thrombi  or  in  the  necrotic  tissue 


138  FOCAL  INFECTION 

of  the  valves  and  heart  walls  of  the  ulcerative  form.  This 
insures  continued  infection  and  increasing  diminished 
resistance  of  the  patient.  Multiple  embolism  and  the 
result  upon  all  the  involved  organs  hastens  the  fatal 
end.    Drug  treatment  is  unavailing. 

Infectious  acute  nephritis  due  to  the  specific  elec- 
tive tissue  affinity  of  certain  bacteria,  especially  mem- 
bers of  the  streptococcus  group,  demands  an  early  re- 
moval of  the  focal  cause.  By  this  means  death  may  be 
prevented  and  if  the  anatomical  injury  of  the  kidney  is 
not  too  great  the  function  may  be  preserved  to  a  degree 
consistent  with  health  for  many  years.  A  woman 
of  thirty  years  under  treatment  for  chronic  arthritis 
at  the  Presbyterian  Hospital  acquired  coryza  and 
an  acute  frontal  sinusitis.  Hemorrhagic  nephritis 
immediately  occurred,  associated  with  some  edema  of 
the  face,  legs  and  dependent  portions  of  the  body. 
Drainage  of  the  infected  sinus  was  followed  by  rapid 
general  improvement  and  a  gradual  disappearance  of 
the  albuminuria  and  the  abnormal  formed  elements  of 
the  urine.  One  month  later  the  urine  and  functional 
tests  for  phthalein,  nitrogen  and  chlorid  output  were  nor- 
mal. A  strain  of  streptococci,  which  was  hemolytic, 
isolated  from  the  exudate  of  the  sinus,  when  injected 
intravenously  into  rabbits  caused  hemorrhagic  ne- 
phritis. 

Many  like  examples  of  improvement  or  recovery  from 
acute  hemorrhagic  nephritis  could  be  reported  from 
our  observation  and  the  experience  of  others  recorded 
in  medical  literature.  So,  too,  one  may  cite  examples 
of  nephritis  which  have  progressed  to  a  hopeless  stage 


TREATMENT  139 

due  to  repeated  anatomical  insults  of  the  kidney  by- 
infectious  microorganisms  from  the  neglected  focus. 

Even  types  of  chronic  nephritis  evidenced  by  albumi- 
nuria, cylindruria  and  more  or  less  hyperarterial  ten- 
sion show  manifest  improvement  by  the  removal  of 
chronic  focal  infection  of  the  dental  alveoli,  tonsils, 
sinuses,  gall-bladder,  appendix  and  pelvic  organs.  A 
rational  after-treatment  consisting  of  a  properly  selected 
diet  and  attention  to  personal  hygiene  is  of  course  an 
important  factor  in  the  improved  condition  of  these 
patients. 

Appendicitis,  acute  and  chronic,  requires  surgical  in- 
tervention to  conserve  life  and  to  obliterate  a  focal  in- 
fection which  may  seriously  infect  other  tissues  through 
the  lymph  channel  or  blood  stream.  The  incidence  of 
appendicitis  may  be  reduced  by  the  prevention  of  focal 
infection  about  the  head  and  by  the  early  removal  of 
existing  foci. 

Acute  and  chronic  cholecystitis  demand  early  surgi- 
cal treatment  to  relieve  pain  and  dyspepsia  and  quite 
as  much  to  remove  a  dangerous  focus  of  systemic  in- 
fection, especially  of  the  myocardium.  Babcock  (40) 
and  others  have  noted  the  improvement  of  clinical  chron- 
ic myocarditis  by  the  drainage  of  a  coexisting  chronic 
cholecystitis.  The  prevention  of  focal  infection  of  den- 
tal alveoli,  tonsils  and  sinuses  and  the  early  removal  of 
existing  infection  at  these  sites  may  diminish  the  inci- 
dence of  cholecystitis  and  of  gall-stones. 

In  the  treatment  of  gastric  and  duodenal  ulcer  the 
experiments  of  Rosenow  demand  the  primary  removal 
of  the  etiologic  foci  of  infection  as  a  means  of  preven- 


140  FOCAL  INFECTION 

tion  of  the  recurrence  of  the  ulcer  through  reinfection. 
A  coincident  rational  medical  management  if  consistent- 
ly carried  out,  as  advised  by  Sippy  (56) ,  may  be  success- 
ful in  healing  the  ulcer.  Surgical  treatment  is  indicated 
when  the  unhealed  ulcer  or  the  scar  produces  deformi- 
ties which  persistently  interfere  with  gastric  and 
intestinal  function  and  also  when  accidents,  like 
perforation  and  medically  unmanageable  hemorrhage, 
occur. 

Recurring  erythema  nodosum  alone  or  as  a  part  of 
the  syndrome  described  by  Osier  (17)  may  be  entirely 
controlled  by  the  removal  of  the  etiologic  infectious 
focus.  A  young  woman  of  twenty- four  years  had  re- 
curring attacks  of  erythematous  nodes  of  the  arms  and 
lower  extremities,  associated  with  mild  arthritis.  She 
suffered  from  a  chronic  maxillary  sinusitis.  Drainage 
of  the  sinus  gave  coincident  freedom  from  the  nodes  and 
arthritis.  After  three  months  a  recurrence  of  the  sys- 
temic disease  proved  to  be  due  to  a  corresponding  re- 
currence of  the  sinus  infection.  Complete  obliteration 
of  the  sinus  infection  has  been  followed  by  the  continued 
absence  of  the  attacks  of  arthritis  and  erythematous 
nodes  for  three  years. 

A  young  married  woman  of  twenty-six  had  recurrent 
attacks  of  erythematous  nodes  and  muscular  soreness 
for  a  year.  She  had  also  frequent  mild  tonsillitis  and 
pharyngitis.  Enucleation  of  the  tonsils  was  followed 
by  the  absence  of  erythematous  nodes  for  nearly  a  year, 
then  a  recurrence.  Re-examination  revealed  the  pres- 
ence of  an  infected  lower  pole  of  one  tonsil.  The  re- 
moval of  the  remaining  portion  of  infected  tonsil  has 


TREATMENT  141 

resulted  in  the  permanent  cessation  of  the  systemic  dis- 
ease. 

The  relation  of  focal  infection  to  acute  pancreatitis 
often  associated  with  cholecystitis  has  been  noted.  Early 
surgical  intervention  to  relieve  the  acute  process  is  im- 
peratively demanded.  Chronic  pancreatitis  is  of  espe- 
cial interest  because  of  the  relation  the  internal  secre- 
tion of  the  gland  bears  to  carbohydrate  metabolism.  The 
probable  infectious  origin  of  chronic  pancreatitis  as  well 
as  the  acute  process  from  streptococcus  foci,  affords  an 
interesting  problem  for  clinical  investigation  in  the  man- 
agement of  diabetes  mellitus.  We  have  removed  exist- 
ing focal  infection  about  the  head  of  diabetic  patients, 
have  inoculated  animals  with  the  isolated  streptococcus 
strains,  and  have  kept  the  patients  under  clinical  ob- 
servation. The  results  have  not  been  uniform  enough 
to  warrant  a  conclusive  statement  at  this  time. 

Chronic  pancreatitis  which  is  etiologically  related  to 
chronic  cholecystitis  and  calculous  cholecystitis  as  de- 
termined by  Opie  (32)  may  disappear  clinically  by  the 
surgical  removal  of  the  etiologic  factors. 

Osteomyelitis  may  not  be  benefited  by  the  removal 
of  the  pyogenic  bacteria  containing  focus  of  the  tonsils, 
jaws,  sinuses  and  other  tissues.  Rationally  the  etiologic 
focus  should  be  removed  coincidentally  with  the  surgi- 
cal treatment  of  the  bone  infection. 

Infectious  thyroiditis  which  occurs  during  a  general 
infection,  like  rheumatic  fever,  may  subside  during  con- 
valescence from  the  general  infection.  When  infectious 
goiter  is  due  to  a  focal  infection  of  the  tonsils  and  alveo- 
lar abscess,  removal  of  the  focus  is  usually  followed  by 


142  FOCAL  INFECTION 

diminution  in  the  size  of  the  gland  and  by  a  disappear- 
ance of  the  symptoms  of  thyroid  intoxication.  This  has 
been  demonstrated  in  many  individuals,  chiefly  young 
women  patients.  The  majority  of  these  women  were 
overworked  and  often  poorly  nourished,  with  resulting 
lowered  immunity  to  the  focal  infection.  Many  of  the 
patients  are  under  continued  observation  and  without 
exception  there  has  been  no  instance  of  relapse  of  the 
goiter  or  of  hyperthyroidism. 

Hematogenous  focal  infection  of  the  nervous  appa- 
ratus, involving  the  gasserian  and  posterior  spinal  root 
ganglia  and  spinal  cord,  affords  confirmation  of  the 
infectious  nature  of  herpes,  of  insular  sclerosis  and 
myelitis  of  the  spinal  cord.  Removal  of  the  primary 
etiologic  foci  of  infection  about  the  upper  air  tract  and 
mouth  may  modify  favorably  the  course  of  the  spinal 
cord  infection. 

The  treatment  of  chronic  types  of  infectious  arthritis 
and  myositis  is  usually  neglected  or  so  irrationally  con- 
ducted that  failure  to  benefit  the  sufferer  is  the  usual 
result.  This  unfortunate  condition  is  due  chiefly  to  a 
want  of  knowledge  by  most  physicians  of  the  principal 
factors  which  cause  the  morbid  tissue  changes.  An 
attempt  was  made  to  explain  these  principles  in  Lecture 
IV. 

In  the  treatment  the  primary  necessity  is  to  obtain 
a  knowledge  of  the  patient's  general  condition  and  to 
locate  existing  foci  of  infection  which  may  have  been 
the  chief  primary  cause,  or  still  continue  to  be  sources 
of  systemic  infection.  The  result  of  rational  manage- 
ment will  depend,  partly  in  any  event,  upon  the  degree 


TREATMENT  143 

and  character  of  the  morbid  tissue  changes  in  the  joints 
and  muscles,  upon  the  command  one  may  have  in  the 
management  and  upon  the  age  of  the  patient.  Destruc- 
tive lesions  of  bones  and  cartilege,  bony  ankylosis,  ex- 
tensive sclerotic  changes  and  atrophy  of  muscles  can- 
not be  repaired.  Indeed  because  of  the  destruction  of 
blood  vessels  and  the  resulting  want  of  nutrition,  con- 
tinued retrograde  metabolism  favors  the  change  of  the 
connective  tissue  group,  tendons,  aponeurosis,  ligament 
and  cartilage  into  bone.  This  is  true  of  all  types 
of  chronic  infectious  non-purulent  arthritis  of  what- 
ever bacterial  type.  Therefore,  if  the  treatment  is  to 
result  in  the  arrest  of  the  disease  with  advanced  mor- 
bid anatomical  changes  or  in  the  recovery  of  those 
with  non-destructive  morbid  tissue  changes,  insti- 
tutional care  is  required  to  insure  the  necessary 
command  of  the  patient  over  a  sufficiently  long  pe- 
riod of  time  to  remove  all  focal  sources  of  infection,  to 
build  up  general  nutrition  and  to  restore  as  nearly  as 
possible  the  blood  circulation  in  the  infected  tissues.  This 
method  of  management  is  necessary  to  stop  the  sources 
of  systemic  infection,  to  build  up  the  body  defenses 
against  the  existing  systemic  infection  and  to  improve 
the  general  and  local  nutrition  as  the  chief  means  of 
arresting  retrograde  metabolism  and  at  the  same  time  to 
promote  resolution  of  the  morbid  infectious  processes. 
Rationally  the  younger  the  patient  the  readier  will  be 
the  response  to  the  management. 

In  the  preliminary  general  examination  one  may  need 
the  aid  of  qualified  specialists  in  the  examination  of  the 
nasopharynx,  ears,  accessory  sinuses,  pelvic  organs  and 


144  FOCAL  INFECTION 

blood,  and  Rontgen  films  of  jaws  and  plates  of  joints 
to  locate  etiologic  infectious  foci  and  to  determine  the 
degree  of  the  joint  changes.  Microscopic  examination 
and  cultures  of  blood,  accessible  exudates  of  joints  and 
of  foci  in  the  head,  pelvis  and  elsewhere  and  of  the  urine 
and  feces  may  give  valuable  information  of  the  char- 
acter of  the  bacterial  infection.  Intravenous  injection 
of  the  nascent  cultures  of  the  bacteria  into  animals  may 
produce  lesions  corresponding  with  the  morbid  changes 
of  the  patients'  tissues.  With  the  consent  of  the  patient 
always,  a  harmless  and,  under  local  anesthesia,  painless 
removal  of  pieces  of  infected  muscle,  joint  capsule, 
fibrous  nodes  and  lymph  nodes  proximal  to  the  infected 
tissues  enables  one  to  study  the  morbid  histology  and 
with  a  proper  technic  to  isolate  the  causative  infectious 
microorganisms  from  the  tissues.  But  important  as  the 
study  of  the  exudates,  tissues  and  bacteria  may  be,  the 
real  and  important  principle  is  to  know  all  that  one 
may  of  the  physical  condition  of  the  patient.  Follow- 
ing this  diagnosis  the  management  includes : 

1.  The  removal  of  all  primary  and,  if  necessary,  all 
secondary  foci  of  infection.  To  make  sure  that  all 
sources  of  focal  infection  have  been  obliterated,  repeated 
examination  should  be  made.  Buried  tonsillar  tissue 
may  be  left  at  the  primary  tonsillectomy.  An  infected 
sinus  may  not  have  been  adequately  treated.  Alveolar 
abscess  may  finally  require  the  extraction  of  the  tooth. 
An  apparently  cured  gonococcus  infection  of  the  pros- 
tate and  seminal  vesicles  may  recur.  Constant  vigilance 
is  necessary  to  insure  the  abolition  of  continued  systemic 
reinfection. 


TREATMENT  145 

2.  To  build  up  the  natural  defenses  of  the  body.  To 
accomplish  this  involves  close  attention  to  important 
principles  including  mental  and  physical  rest,  nourish- 
ing food,  restorative  tonics  when  indicated,  cheerful  en- 
vironment, good  air  and  sunshine  and  with  some  patients 
the  use  of  suitable  bacterial  antigens  as  vaccines  to  stim- 
ulate the  formation  of  specific  antibodies  in  the  tissues 
of  the  patient.  Mental  and  physical  rest  must  be  ra- 
tionally supervised  to  meet  the  idiosyncrasies  of  the  indi- 
vidual. Isolation  and  continuous  bed  confinement  may 
be  exchanged  for  open  ward  and  partial  chair  treat- 
ment to  meet  the  viewpoint  of  the  patient  and  thus  pro- 
mote the  most  efficient  rest  of  mind  and  body.  This 
absolute  rest  must  be  maintained  until  in  febrile  cases 
all  fever  shall  have  disappeared  and  also  until  the  severe 
soreness  of  the  joints  and  muscles  aggravated  by  motion 
shall  have  diminished,  for  until  then  the  exercise  of  in- 
fected tissues^  lowers  the  natural  resistance  to  infection 
and  thereby  increases  the  infection  of  the  joints  and 
muscles.  Often  the  temporary  application  of  restrain- 
ing bandages,  splints  and  casts  may  favor  the  diminu- 
tion of  the  local  infection.  The  usually  poor  general 
nutrition  of  patients  with  chronic  infectious  arthritis 
calls  for  a  generous  mixed  diet  including  an  abundance 
of  fats,  oils,  green  vegetables  and  fruits.  The  emaciated 
tissues  demand  a  full  allowance  of  protein-containing 
food,  both  animal  and  vegetable.  A  plentiful  amount 
of  water,  milk,  buttermilk,  cream  and  fruit  juices  must 
be  taken. 

When  necessary,  hematinic  and  other  tonics,  laxa- 
tives, and  simple  analgesic  palliatives,  such  as  the  sali- 


146  FOCAL  INFECTION 

cylic  acid  compounds,  may  be  judiciously  given.  There 
are  no  specific  drugs  to  be  used  and  narcotics  should 
be  avoided  in  these  chronic  diseases. 

The  mental  depression  of  this  class  of  patients  re- 
tards improvement,  hence  the  need  of  a  constant,  cheer- 
ful environment  and  an  optimistic  attitude  of  all  who 
come  in  contact  with  them. 

With  the  sources  of  systemic  infection  obliterated,  and 
the  existing  systemic  infection  diminished  or  entirely 
controlled  by  the  management  described,  other  measures 
must  be  added  to  the  treatment  which  may  stop  further 
retrograde  metabolism,  and  in  favorable  conditions 
may  result  in  the  restoration  of  normal  anatomical  and 
functional  conditions  of  the  tissues  of  the  joints  and 
muscles. 

These  measures  are  so  important  that  the  failure 
to  apply  them  adequately  means  failure  in  the  whole 
management.  The  object  of  their  use  is  to  attempt  to 
restore  nutrition  to  the  starved  tissues  of  joints  and 
muscles  which  have  been  deprived  more  or  less  of  blood 
and  oxygen  by  the  embolic  mode  of  repeated  infection 
from  the  primary  focus,  for  as  long  as  the  infected  tis- 
sues are  starved,  conditions  exist  which  are  favorable 
to  continued  infection  and  furthermore,  local  malnutri- 
tion leads  to  retrograde  tissue  metabolism. 

In  addition  to  the  measures  already  advised  to  in- 
crease the  general  nutrition,  the  local  malnutrition  may 
be  wholly  or  partly  overcome  by  an  improvement  of 
the  general  and  local  blood  circulation.  The  measures 
consist  of  hydrotherapy,  active  and  passive  exercise, 
local  application  of  superheated  dry  air  and  the  Bier 


TREATMENT  147 

blood  congestion  method  by  the  application  of  the  rub- 
ber bandage. 

Hydrotherapy  in  the  form  of  alternating  hot  and 
cold  shower  or  spray  baths,  applied  daily  for  a  few 
minutes,  flushes  the  blood  to  all  the  parts  of  the  body 
without  fatigue  to  the  patient.  If  the  force  with  which 
the  water  strikes  the  body  is  relatively  high,  the  im- 
provement of  the  circulation  is  greater.  The  tonic 
effect  upon  the  circulatory  organs  of  the  application  of 
cold  water  to  the  skin  is  well  known.  A  cold  plunge 
bath  is  disagreeable  to  these  enervated  patients.  The 
alternating  hot-cold  spray  repeated  several  times  in  a 
few  minutes,  is  borne  without  complaint,  and  the  result 
is  quite  as  good  as  the  use  of  the  cold  bath  alone.  In 
the  absence  of  facilities  for  applying  shower  or  spray 
baths,  salt  glows  and  alcohol  rubs  may  be  utilized  as 
poor  substitutes  of  the  cold  bath. 

Passive  exercise  of  joints  and  muscles  may  be  given 
by  nurses  or  more  efficiently  by  individuals  trained  to 
give  massage.  Mechanical  aids  in  the  form  of  the  Zan- 
der apparatus  if  rationally  used  give  good  results. 

Active  calisthenic  exercises  may  be  so  taught  that  un- 
der proper  supervision  each  patient  will  have  the  bene- 
fit of  periods  of  exercise  modified  to  meet  individual 
conditions. 

Other  active  exercise,  like  walking,  riding,  driving, 
swimming  and  gymnastic  work,  may  be  taken  up  at  the 
proper  time.  An  individual  qualified  by  education  and 
experience  should  have  the  supervision  of  the  treatment 
by  baths,  and  mechanotherapy.  Every  general  hospital 
should  have  a  mechanotherapeutic  department  with  a 


148  FOCAL  INFECTION 

qualified  director  for  the  treatment  at  the  right  stage 
of  the  management  of  the  large  number  of  patients,  in 
all  communities,  who  suffer  from  chronic  infectious  ar- 
thritis and  of  other  chronic  diseases.  If  rationally  and 
efficiently  managed  many  would  be  restored  to  health, 
while  in  others  with  more  advanced  morbid  anatomical 
changes  the  further  progress  of  disease  would  be  more 
or  less  checked  and  an  improvement  of  function  would 
be  gained. 

SERUM  AND  VACCINE  THERAPY 

Serum  Therapy 

The  prophylactic  and  therapeutic  use  of  antitoxic 
sera  in  diphtheria  and  tetanus  is  established  upon  a  sci- 
entific basis.  The  specific  neutralization  of  the  poison 
excreted  by  the  exotoxic  bacillus  of  diphtheria  and  bacil- 
lus of  tetanus,  when  the  respective  antitoxic  serum  is 
properly  administered,  may  be  accurately  ascertained  by 
clinical  and  laboratory  methods. 

The  use  of  specific  antisera  in  the  treatment  of  dis- 
eases caused  by  endotoxic  bacteria  has  been  far  from 
successful.  The  principle  upon  which  the  value  of  an- 
tisera is  based,  is  that  when  injected  subcutaneously, 
there  will  be  aroused  in  the  body  of  the  patient  specific 
defensive  forces,  in  the  form  of  antibodies,  leukocytic 
phagocytosis  and  bactericidal  substances  which  may  fa- 
vorably modify  the  course  of  the  disease.  In  epidemic 
cerebrospinal  meningitis  the  specific  antimeningococcal 
serum  of  Flexner,  when  in j  ected  directly  into  the  spinal 
subarachnoid  space,  apparently  has  specific  bactericidal 
properties.     The  injected  serum  probably  arouses  tis- 


TREATMENT  149 

sue  reactions,  which  mobilizes  the  defenses  of  the  body, 
increasing  cellular  phagocytosis,  digestion  of  the  invad- 
ing meningococci  and  even  acting  directly  as  a  bac- 
tericide. Other  therapeutic  antisera  obtained  by  im- 
munizing animals  with  strains  of  the  streptococcus, 
pneumococcus,  bacillus  of  dysentery  and  other  endo- 
toxic  bacteria  have  not  given  uniform  results.  The  fail- 
ure of  these  sera  generally  now  is  recognized  to  be  due 
to  several  factors,  including  the  existence  of  variant 
strains  of  bacteria  which  may  not  be  differentiated  mor- 
phologically. Moreover,  there  may  be  a  marked  dif- 
ference in  the  various  strains  in  pathogenicity  and  viru- 
lence and  in  the  tissue  reactions  of  the  infected  individ- 
ual. Each  strain  may  arouse  specific  effects  and  the 
results  thereof  will  be  influenced  only  by  the  therapeutic 
serum  obtained  from  an  animal  immunized  with  a  like 
strain.  This  principle  has  been  successfully  utilized  by 
Cole  and  his  co-workers  in  pneumonia.  They  have  clas- 
sified the  pneumococcus  into  four  types,  of  which  types 
I,  II  and  III  represent  single  specific  strains  and  type 
IV  a  group  of  strains  unlike  the  first  three  types.  The 
antiserum  must  be  prepared  by  immunizing  an  animal 
with  the  type  of  pneumococcus  which  is  to  be  attacked. 
The  same  principle  has  been  proved  to  exist  in  reference 
to  the  pathogenic  strains  of  streptococci  and  of  the 
strains  of  the  bacillus  of  dysentery.  The  principle  of 
the  necessary  possession  of  "type"  specificity  of  the  bac- 
teria used  in  the  production  of  antisera  to  obtain  any- 
thing like  satisfactory  therapeutic  results  has  been  ap- 
parently established.  While  it  may  not  prove  to  be  a 
principle  to  be  applied  to  the  preparation  of  antisera 


150  FOCAL  INFECTION 

of  all  endotoxic,  pathogenic  bacteria,  perhaps  to  a  few 
only,  yet  there  is  in  its  adoption  the  hope  that  a  broader 
field  of  specific  antiserum  treatment  may  be  developed. 
In  our  study  of  focal  and  systemic  infections  we  used 
the  antiserum  of  the  horse  immunized  with  strains  of 
streptococcus  viridans  in  the  treatment  of  streptococcus 
viridans  endocarditis  and  in  chronic  arthritis  without 
notable  good  effect.  Apparently  unavoidable  anaphy- 
lactic shock  and  other  objectionable  effects  compelled 
us  to  abandon  its  use.  Therefore,  the  production  of  and 
the  use  of  antisera  in  the  treatment  of  diseases  due  to 
focal  infection  present  problems  which  present  knowl- 
edge may  not  solve. 

Vaccine  Therapy 

We  know  that  a  degree  of  immunity  to  some  infec- 
tious diseases  may  be  produced  in  man  and  animals  by 
inoculation  with  non-lethal  doses  of  living  or  dead  path- 
ogenic bacteria.  In  a  few  diseases,  a  mild  form  of  in- 
fection or  intoxication  is  produced  by  the  inoculation 
with  resulting  immunity  of  variable  duration.  Attenu- 
ation of  the  virulence  of  living  virus  used  for  inocula- 
tion has  been  successfully  practiced  to  produce  a  mild 
disease  which  affords  protection  to  the  protean  malady. 
Vaccinia  in  man  produced  by  inoculation  with  cowpox 
protects  against  variola.  Inoculation  with  living  or 
dead  typhoid  bacteria  and  paratyphoid  bacilli  with 
proper  technic  will  afford  immunity  of  variable  time 
duration  to  typhoid  and  paratyphoid  fevers.  These  ex- 
amples of  the  use  of  vaccines  in  prophylaxis  have  a  very 
limited  application  in  practice.     Probably  the  field  of 


TREATMENT  151 

application  may  become  broader  when  we  finally  recog- 
nize the  specific  etiologic  microorganisms  of  all  infec- 
tious diseases  which  usually  give  a  lasting  immunity  by 
one  attack.  Then,  as  in  typhoid  fever,  prophylactic 
vaccination  may  become  of  the  greatest  use  in  preven- 
tive medicine. 

Vaccination  with  attenuated  virus  during  a  long  in- 
oculation stage  of  infection,  as  successfully  practiced 
by  Pasteur  in  man  bitten  by  animals  suffering  with  ra- 
bies, will  probably  not  be  applicable  in  other  infections 
which  have  comparatively  shorter  incubation  stages. 
The  present  use  of  therapeutic  vaccines  is  based  upon 
less  stable  scientific  principles.  In  1902  Wright  evolved 
the  use  of  autogenous  vaccines  in  chronic  infectious  dis- 
eases. He  believed  that  the  natural  defenses  of  the 
body,  exhausted  by  long  infection,  would  be  increased 
and  mobilized  by  inoculation  with  microorganisms  of 
the  same  type  and  kind  which  caused  the  chronic  disease. 
He  judged  the  improvement  in  the  defensive  forces  of 
the  patient's  body  after  autogenous  vaccination  by  esti- 
mating the  opsonins  in  the  patient's  blood.  He  argued 
that  with  an  increase  of  specific  antibodies  in  the  blood 
of  the  patient,  the  fibrinoplastic  exudative  barrier  sur- 
rounding local  infectious  processes,  which  afforded  pro- 
tection to  the  localized  bacteria,  would  be  broken  down 
by  the  mobilization  of  immune  substances.  The  bac- 
teria so  exposed  would  then  be  readily  overcome.  Thus 
furunculosis  of  the  skin,  due  usually  to  a  staphylococcus, 
was  more  readily  overcome  by  autogenous  staphylococ- 
cus vaccine. 

It  would  seem  rational,  too,  that  a  general  chronic 


152  FOCAL  INFECTION 

infectious  process  would  be  more  readily  overcome  by 
the  use  of  an  autogenous  vaccine  which  would  increase 
the  natural  defenses  of  the  body  which  have  become  ex- 
hausted by  the  long  battle  with  the  invading  bacteria. 
Unfortunately  the  question  involves  many  unknown  fac- 
tors. A  certain  type  of  pathogenic  bacterium,  used  as 
an  antigen,  may  excite  the  formation  of  antibodies  in 
the  nature  of  opsonins,  agglutinins,  precipitins,  leukocy- 
tosis, phagocytosis  and  other  offensive  or  defensive  proc- 
esses, but  we  may  not  depend  upon  a  similar  result  with 
other  pathogenic  bacteria  etiologically  related  to  other 
infectious  diseases.  We  cannot,  from  present  knowl- 
edge, definitely  expect  the  same  tissue  reactions  and  re- 
sulting formation  of  immune  substances  in  man  and 
laboratory  animals  infected  with  the  same  type  of  in- 
fectious bacteria.  Indeed  the  resulting  tissue  reactions 
and  formation  of  defensive  and  offensive  substances  to 
a  strain  of  pathogenic  microorganisms  may  differ  in  de- 
gree and  kind  in  human  beings,  dependent  on  age,  race, 
occupation  and  other  factors.  Variations  of  type  of 
strains  of  pathogenic  bacteria  with  corresponding  dif- 
ferences in  the  tissue  reactions  of  infected  individuals, 
is  an  important  factor  in  immunological  experimenta- 
tion. We  know  that  the  pneumococcus  and  strains  of 
streptococci  not  only  differ  in  type,  but  also  differ  in 
virulence,  and  that  each  type  probably  arouses  defensive 
and  offensive  forces  in  the  infected  individual,  differing 
more  or  less  for  each  type;  and  possibly  the  tissue  re- 
actions are  still  further  modified  by  the  degree  of  viru- 
lence of  the  invading  bacteria.  Pathogenic  bacteria  may 
possess  a  mono-  or  polytropism ;  that  is,  an  elective  affin- 


TREATMENT  153 

ity  for  a  certain  kind  of  tissue  or  for  several  kinds  of 
tissues.  Therefore,  if  specific  vaccine  is  necessary  to 
arouse  specific  immune  substances  to  combat  offensively 
or  defensively  the  invading  infectious  bacteria,  it  implies 
the  use  of  an  autogenous  antigen.  In  this  sense  an  au- 
togenous vaccine  means  the  use  of  dead  bacteria,  proved 
to  be  of  the  same  specific  type  in  virulence  and  tropism 
as  that  which  causes  the  infection  of  the  individual  who 
receives  the  vaccine.  In  chronic  infectious  diseases,  it  is 
often  difficult  to  isolate  definitely  the  microorganisms 
which  are  the  real  etiologic  factors  in  a  given  case. 
Without  an  accurate  bacterial  diagnosis  one  is  unable 
to  discuss  the  other  vexatious  problems  which  must  be 
considered  in  the  elaboration  and  use  of  the  autogenous 
vaccine. 

In  our  work  we  have  isolated  the  suspected  bacteria 
from  the  blood,  lymph  nodes,  fibrous  nodes,  joint  exu- 
dates, joint  tissues,  muscles,  skin  and  other  infected  tis- 
sues of  patients.  To  ascertain  the  tissue  tropism  we 
have  injected  animals  intravenously  and  from  the  in- 
fected tissues  of  the  experimental  animals,  have  again 
isolated  the  bacteria.  Vaccines  have  been  prepared  from 
cultures  made  from  the  microorganisms  isolated  from 
patients  and  also  from  the  cultures  derived  from  pa- 
tients after  animal  passage  with  especial  regard  to  tissue 
tropism.  We  have  also  sensitized  some  of  these  vac- 
cines with  antiserum. 

We  have  used  these  autogenous  vaccines  in  the  treat- 
ment of  many  types  of  chronic  infectious  disease.  More 
than  five  hundred  patients  suffering  with  infectious  ar- 
thritis have  received  the  vaccines  subcutaneously  in  doses 


154  FOCAL  INFECTION 

varying  from  10,000,000  to  2,000,000,000  and  more, 
given  every  five  to  seven  days,  and  in  rare  instances 
daily.  The  focal,  local  and  general  reaction  of  patients 
was  carefully  noted.  For  two  years  the  opsonic  index 
and  the  phagocytic  index  of  each  patient  were  estimated 
painstakingly  before  and  after  each  vaccination. 

The  difficulty  of  estimating  the  opsonins  and  the  final 
conclusion  that  the  opsonic  index  obtained  by  the  most 
careful  technic  is  unreliable  led  us  to  abandon  that 
method  of  estimating  the  results  of  autogenous  vacci- 
nation. 

In  place  thereof  we  managed  some  patients  with  and 
some  without  vaccination,  but  all  of  them  upon  the  same 
hygienic  treatment.  The  final  result  was  quite  as  satis- 
factory without  as  with  vaccine,  in  patients  suffering 
with  chronic  infectious  arthritis  and  acute  rheuma- 
tism. 

Patients  suffering  with  chronic  streptococcus  viridans 
endocarditis  were  not  benefited  by  autogenous  vaccines. 
Indeed  I  believe  some  of  them  were  made  distinctly 
worse  when  moderately  large  doses  of  vaccines  were 
used. 

The  problems  which  confront  the  clinician  in  the  use 
of  therapeutic  vaccines,  must  be  solved  by  the  immunolo- 
gist.  The  views  of  Theobald  Smith  (39),  Richard  M. 
Pearce  (38)  and  others  in  regard  to  therapeutic  vac- 
cines should  be  read  by  every  clinician. 

Based  upon  the  work  of  Wright,  but  disregardful 
of  the  principles  developed  by  him,  therapeutic  vacci- 
nation has  progressed  in  this  country  into  an  irrational 
fad  which  is  intensified  and  made  degrading  to  the  med- 


TREATMENT  155 

ical  profession  and  harmful  to  the  patients  by  commer- 
cial greed. 

We  are  forgetful  of  the  principles  of  medical  practice 
of  our  fathers.  They  recognized  the  influence  of  old 
age,  exposure  to  extreme  cold,  poverty  and  poor  nutri- 
tion, physical  and  mental  exhaustion,  faulty  personal 
hygiene  and  other  debility-producing  factors  in  the  cau- 
sation and  also  in  the  prolongation  of  infectious  and 
other  diseases.  They  also  recognized  the  necessity  of 
the  removal  as  far  as  possible  of  all  these  contributory 
etiologic  factors  in  the  management  of  the  patient. 
The  modern  vaccinationist  pins  his  faith  on  the  adver- 
tised specific  virtues  of  stock  vaccines,  which  he  may  em- 
ploy in  polyvalent  form  to  insure  a  sure-shot  effect. 
He  believes  vaccines  will  arouse  specific  defenses  in  the 
tissues  of  the  patient  in  spite  of  all  contributory  etio- 
logic factors  of  disease.  Therefore,  the  rational  diet, 
proper  baths,  passive  and  active  exercise,  correction  of 
personal  uncleanliness  and  alcohol  misuse  are  neglected. 
The  practitioner  usually  is  ignorant  of  all  laws  of  im- 
munology. It  is  this  want  of  knowledge  which  makes 
him  believe  the  ridiculous  statements  made  by  the  manu- 
facturers of  vaccines. 

Modern  experimental  investigation  of  the  physiologic 
action  of  drugs  has  done  much  to  restrict  the  abuse  of 
drug  therapy  of  the  past.  So,  too,  must  the  practitioner 
be  made  acquainted  with  what  we  know  and  do  not  know 
of  immunology.  We  must  restrict  the  therapeutic  use 
of  bacterial  antigens  to  those  conditions  which  the 
known  laws  of  immunity  and  scientific  clinical  experi- 
ence have  proved  to  be  safe  and  of  value. 


156  FOCAL  INFECTION 

The  Therapeutic  Use  of  Non-specific  Protein  Anti- 
gens Injected  Intravenously 

In  recent  time  the  intravenous  injection  of  non-spe- 
cific proteins  (bacterial  and  others)  has  been  used  in 
the  treatment  of  both  acute  and  chronic  infectious  dis- 
ease. The  phenomena  aroused  by  a  proper  intra- 
venous dosage  consist  of  a  chill  followed  by  high  fever, 
great  general  discomfort,  usually  a  relatively  slow  pulse 
rate,  leukocytosis  sometimes  of  a  high  degree,  not  in- 
frequently preceded  by  an  immediate  leukopenia.  Gay 
and  Chickering  (49)  have  used  the  protein,  non-toxic 
remnant  of  the  typhoid  bacillus  by  intravenous  injec- 
tion in  the  treatment  of  typhoid  fever.  The  characteris- 
tic phenomena  noted  above  resulted.  When  used  after 
the  first  week  of  typhoid  fever,  the  reaction  was  fol- 
lowed by  a  critical  fall  of  the  temperature  and  conva- 
lesence  was  established  in  41.5  per  cent.  A  gradual  fall 
of  temperature  occurred  with  abbreviation  of  the  course 
in  24.5  per  cent,  and  no  permanent  benefit  occurred  in 
34  per  cent,  of  the  patients  treated.  We  have  used  the 
non-toxic  protein  remnant  of  pneumococci  obtained  by 
autolysis  of  the  bacteria,  first  suggested  by  E.  C.  Rose- 
now,  in  pneumonia.  When  injected  intravenously,  the 
typical  phenomena  occurred  with  apparent  beneficial 
effect,  which  was  most  marked  if  used  early  in  the 
course  of  the  disease. 

In  acute  rheumatism  and  also  in  chronic  infectious  ar- 
thritis, astonishing  beneficial  effects  have  been  noted 
in  a  few  instances  from  the  intravenous  injection  of  ty- 
phoid, of  colon  and  of  other  non-specific  protein  anti- 


TREATMENT  157 

gens.  Jobling  and  Peterson  (48)  injected  animals  in- 
travenously with  dead  bacteria  and  found  that  non-spe- 
cific ferments  were  mobilized.  They  believe  that  these 
ferments  are  bactericidal  and  that  at  the  same  time  toxic 
substances  are  rendered  non-toxic.  The  suggestion  has 
been  made  that  the  severe  reaction  caused  by  the  intra- 
venous injection  of  a  foreign  protein,  is  followed  by  a 
condition  of  refraction  (anti-anaphylaxis)  and  the  or- 
ganism fails  to  react  to  the  invading  bacteria.  Jobling 
believes  that  it  will  be  possible  in  the  near  future  to  use 
intravenously  the  non-toxic  portion  of  protein  to  ex- 
cite the  mobilization  of  the  helpful  ferments  without  the 
painful,  disagreeable  and  even  dangerous  clinical  phe- 
nomena which  attend  the  intravenous  use  of  unmodified 
protein  antigen.  The  mode  of  action  of  the  non-specific 
albumose  antigens,  injected  intravenously,  is  not  well 
understood.  Their  use  in  acute  and  chronic  infectious 
diseases  affords  a  fruitful  field  of  combined  research  by 
the  immunologist  and  clinician. 


BIBLIOGRAPHY 

1.  Bass,  C.  C,  and  Johns,  F.   M.  "Pyorrhea  Dentalis  and 

Alveolaris."     The  Jour.  A.  M.  A.,  1915,  LXIV,  553. 

2.  Barrett,   M.    F.      Preliminary    Report,   Dental   Cosmos, 

1914,  LVI,  948. 

3.  Smith,  Allen  J.,  Middleton,  W.  S.,  and  Barrett,  M.  F. 

"Tonsils  as  a  Habitat  of  Oral  Endamebas,"  The 
Jour.  A.  M.  A.,  1914,  LXIII,  1746. 

4.  Sugimura,  S.     "Ueber  die  Beteilung  der  Ureteren  an  den 

akuten  Blasen  entziindengen  nebst  Bemerkungen  iiber 
ihre  Fortleitung  durch  die  Lymphbahnen  der  Ure- 
teren."    Virchow  Arch.,  CCVI,  20. 

5.  Franke,  Carl.     "Die  Koliinfection  des  Harnapparats  und 

deren  Therapie."  Ergabniss  d.  Chirurg.  u.  Ortho- 
pod.,  1913,  VII,  671. 

6.  Dick,  Geo.  F.,  and  Dick,  Gladys  R.     "The  Bacteriology 

of  the  Urine  in  Non-suppurative  Nephritis."  The 
Jour.  A.  M.  A.,  1915,  LXV,  6. 

7.  Kolle,    W.,    and    Wassermann,    A.      "Latency    of    In- 

fectious Bacteria."  Hand  Buch  der  Path.  Mikro- 
organismen,  1903,  I,  147. 

8.  Rosenow,  E.  C.   "Immunological  and  Experimental  Studies 

on  Pneumococcus  and  Streptococcus  Endocarditis" 
(Chronic  Septic  Endocarditis) .  Jour.  Inf.  Dis.,  1909, 
VI,  245. 

.     "A  Study   of  Pneumococci   from  Cases   of  Infectious 

Endocarditis."    Jour.  Inf.  Dis.,  1910,  VII,  411. 

.     "Immunological  Studies  in  Chronic  Pneumococcus  En- 
docarditis."   Jour.  Inf.  Dis.,  1910,  VII,  429. 

.     "Transmutation  Within  the  Streptococcus-Pneumococ- 

cus  Group."    Jour.  Inf.  Dis.,  1914,  XIV,  I. 
159 


160  BIBLIOGRAPHY 

Rosenow,  E.  C.  "The  Etiology  of  Acute  Rheumatism,  Ar- 
ticular and  Muscular."  Jour.  Inf.  Dis.,  1914,  XIV, 
61. 

„     "The  Bacteriology  of  Appendicitis  and  Its  Production 

by  Intravenous  Injection  of  Streptococci  and  Colon 
Bacilli."    Jour.  Inf.  Dis.,  1915,  XVI,  240. 

.  "The  Etiology  and  Experimental  Production  of  Ery- 
thema Nodosum."     Jour.  Inf.  Dis.,  1915,  XVI,  367. 

8.  Rosenow,  E.  C,  and  Sanford,  A.  H.  "The  Bacteriology 
of  Ulcer  of  the  Stomach  and  Duodenum  in  Man." 
Jour.  Inf.  Dis.,  1915,  XVII,  219. 

8.  Rosenow,  E.  C.  "The  Newer  Bacteriology  of  Various 
Infections  as  Determined  by  Special  Methods."  The 
Jour.  A.M.  A.,  1914,  LXIII,  903. 

.     "Bacteriology  of  Cholecystitis  and  Its  Production  by 

Injection  of  Streptococci."  The  Jour.  A.  M.  A., 
1914,  LXIII,  1835. 

8.  Rosenow,  E.  C,  and  Ofterdal,  Sverri.  "The  Etiology 
and  Experimental  Production  of  Herpes  Zoster." 
The  Jour.  A.  M.  A.,  1915,  LXIV,  1968. 

8.  Rosenow,   E.    C.      "Iritis    and   Other   Ocular   Lesions    on 

Intravenous  Injection  of  Streptococci."  Jour.  Inf. 
Dis.,  1915,  XVII,  403. 

9.  Billings,  Frank.     "Chronic  Focal  Infections  and  Their 

Etiologic    Relations    to    Arthritis    and    Nephritis." 

Arch.  Int.  Med.,  1912,  IX,  484. 
.      "Chronic  Focal  Infections   as   a  Causative  Factor  in 

Chronic  Arthritis."    The  Jour.  A.M.  A.,  1913,  LXI, 

819. 
.     "Chronic   Infectious   Endocarditis."      The  Arch.   Int. 

Med.,  1909,  IV,  409. 
.     "Clinical  Aspect  and  Medical  Management  of  Arthritis 

Deformans."    III.  Med.  Jour.,  1914,  XXV,  11. 
.     "Focal  Infection:  Its  Broader  Application  in  the  Etiol- 
ogy of  General  Disease."     The  Jour.  A.  M.  A.,  1914. 

LXIII,  899. 


BIBLIOGRAPHY  161 

Billings,  Frank.  "Systemic  Diseases  of  Focal  Origin." 
Forchheimer's  Therapeusis,   191 4-,  V,  169. 

10.  Schottmuller,   H.      "Die  Artuntersuchendung  der   fur 

Menschen    Pathogenen     Streptokokken    durch     Blu- 

tagar."      Munch.    Med.    Wchnschr.,    1903,   L,    849. 
.      "Ziir    Aetiologie    der    Pneumonie    Cruposa."      Munch. 

Med.  Wchnschr.,  1905,  LII,  30. 
.     "Endocarditis  Lenta."    Munch.  Klin.  Wchnschr.,  1910, 

880  (quoted  by  Libman). 

11.  Cole,  Rufus,  and  Dochez,  A.  R.     "Report  of  Studies 

in  Pneumonia."  Trans.  Assn.  Am.  Phys.,  1913, 
XXVIII,  606. 

12.  Haessli,    Hans.       "Der    Verhalten    der    Streptokokken 

Gegeniiber  Plasma  und  Serum  und  ihre  Umzuchtung." 
Mitth.  a.  d.  Hamb.  Staats  Kranhenamst,  1910,  XL, 
10. 

13.  Forssner,   G.      "Renale   Lokalisation   nach   intravenosen 

Injektionen  mit  einer  dem  Nierengewebe  experimental 
angepassten  Streptokokken  cultur."  Nord.  Med. 
ArJciv.,  1902,  XXXV,  1-56. 

14.  Poynton,  F.    J.,  and  Paine,  A.     "The  Etiology  of  Rheu- 

matic Fever."     The  Lancet,  1900,  II,  861. 

.     "A  Further  Contribution  to  the  Study  of  Rheumatism ; 

the  Experimental  Production  of  Appendicitis  by  the 
Intravenous  Inoculation  of  the  Diplococcus."  The 
Lancet,  1911,  II. 

.     "Observations  Upon  the  Arthritis  Produced  in  Rabbits 

by  the  Intravenous  Inoculation  of  a  Diplococcus  Iso- 
lated from  Cases  of  Rheumatism."  Trans.  Path.  Soc, 
London,  1904. 

.     "Observations  Upon  Certain  Forms  of  Arthritis."    Br. 

Med.  Jour.,  1902,  II,  1414. 

.     "The  Pathogenesis  of  Rheumatic  Fever."     Trans.  Path. 

Soc,  London,  1901. 

.  "The  Relation  of  Malignant  to  Rheumatic  Endocar- 
ditis."   The  Lancet,  1902,  I,  1036. 


162  BIBLIOGRAPHY 

Poynton,  F.  J.,  and  Paine,  A.  "Remarks  on  the  Infec- 
tious Nature  of  Rheumatic  Fever,  Illustrated  by 
the  Study  of  a  Fatal  Case."  Br.  Med.  Jour., 
1904,  I. 

.     "Some  Further  Investigations  and  Observations  Upon 

the  Pathology  of  Rheumatic  Fever."  The  Lancet, 
1910, 1,  1524. 

15.  Beattie,    James.    "Acute    Rheumatism."      Edinb.    Med. 

Jour.,  1904. 

16.  Walker,  E.  W.  A.,  and  Ryffel,  J.  H.     "The  Pathology 

of  Acute  Rheumatism  and  Allied  Disorders."  Br. 
Med.  Jour.,  1903,  II,  659. 

17.  Osler,  Wm.     "Chronic  Infectious  Endocarditis."     Quar. 

Jour.  Med.,  1909,  II,  219. 

.     "On    the   Visceral    Complications    of   Erythema   Exu- 

dativum  Multiforme."  Am.  Jour.  Med.  Sci.,  1895, 
CX,  629. 

18.  Horder,  Thomas  J.      "Infective  Endocarditis."      Quar. 

Jour.  Med.,  1909,  II,  289. 

19.  Libman,    E.,    and    Celler,    H.    L.      "The    Etiology    of 

Subacute  Infective  Endocarditis."  Jour.  Am.  Med. 
Sci.,  1910,  CXL,  516. 

20.  Libman,  E.     "A  Study  of  the  Lesions  of  Subacute  Bac- 

terial Endocarditis  with  Peculiar  Reference  to  Heal- 
ing or  Healed  Lesions,  with  Clinical  Notes."  Jour. 
Am.  Med.  Sci.,  1912,  CXLIV,  313. 

21.  Herrick,  James  B.     "The  Healing  of  Ulcerative  Endo- 

carditis."   Med,  News,  1902,  XXXI,  10. 

22.  Lenhartz,    H.       "Ueber    die    Septische    Endocarditis." 

Munch.  Med.  Wchschr.,  1901,  XL VIII,  28. 

23.  Baehr,  Geo.     "Glomerular  Lesions  of  Subacute  Bacterial 

Endocarditis."  Jour.  Am.  Med.  Sci.,  1912,  CXLIV, 
327. 

24.  Lohlein,  M.     "Ueber  hamorrhagische  Nieren  Affektionen 

bei  Chronischer  Ulcerosen  Endokarditis."  Med. 
Klin,,  1910,  VI,  10. 


BIBLIOGRAPHY  103 

25.  Kretz,    Richard.      "Angina    und    Septische    Infektion." 

Zeitschr.  f.  Heilkund.,  1907,  XXVIII,  296. 

26.  Cannon,  Dr.      "Ueber  die  Frage  der  hamatogenen  In- 

fektion  bei  Appendicitis  und  Cholecystitis."  Deutsch. 
Zeitschr.  f.  Chir.,  1908,  XCV,  21. 

27.  Ghon,  A.,  and  Namba,  K.     "Zur  Frage  iiber  die  Genese 

der  Appendicitis."  Beitrag.  z.  Path.  Anat.  u.  z. 
Algem.  Path.,  1912,  LII,  130. 

28.  Adrian,  C.     "Die  Appendicitis  als  Folge  einer  Allgemei- 

nerkrankung."  Klinisch.es  und  Experimentelles.  Mit~ 
teil,  a.  d.  Grenzgeb.  d.  Med.  u.  Chir.,  1901,  VII, 
407. 

29.  Heyde,     M.        "Bakteriologische     und     Experimented 

Untersuchungen  zur  Aetologie  der  Wurmfort- 
satzentziingen  (mitt  besondere  Beriicksichtigung  der 
Anaeroben  Bakterien)."  Beitr.  z.  Klin.  Chir.,  1911, 
LXXVI,  I. 

30.  Aschoff,  L.      "Pathogenese   und  Atiologie   der  Appen- 

dicitis." Ergebnisse  d.  Inner  Med.  u.  Kinderheil- 
kund,  1912,  IX,  1. 

31.  Vincent,  H.      "Sur  la  thyroidism  dans  la  rheumatisme 

aigu,  et  sur  l'origine  rheumatismale  de  certain  cas 
du  goitre  exophthalmique."  Compt.  rend.  Soc.  de 
Biol.,  1907,  LXIII,  389. 

.     "Rapports  de  la  maladie  Basedow  avec  la  rheumatisme 

aigu."  Bull,  de  la  Soc.  Med.  de  Paris,  1907,  XXIV, 
1286 ;  Semaine  Med.,  1907,  Mar.  20,  143,  Ibid.,  1907, 
Nov.  21,  575;  Ibid.,  1908,  Jan.  1,  47;  Ibid.,  1908, 
Oct.  28,  527. 

32.  Opie,    E.    L.      "The    Etiology    of    Acute    Hemorrhagic 

Pancreatitis."     J.  H.  H.  Bull,  1901,  182. 

33.  Davis,   D.    J.      "Bacteriological    and   Experimental   Ob- 

servations on  Focal  Infection."  Arch.  Int.  Med., 
1912,  505. 

34.  Jackson,    Lelia.      "Experimental    Rheumatic    Myocar- 

ditis."    Jour.  Inf.  Dis.,  1912,  XI,  240. 


164  BIBLIOGRAPHY 

35.  Le  Count,  E.   R.,   and  Jackson,  Lelia.     "The  Renal 

Changes  in  Rabbits  Inoculated  with  Streptococci." 
Jour.  Inf.  Dis.,  1914,  XV,  389. 

36.  Irons,  Ernest  E.    "Bacteriology  and  Immunity.    Studies 

in  Gonococcal  Immunit}'."  Trans.  XVIIth  Internat. 
Med.  Cong.,  1913,  87. 

37.  Irons,   Ernest   E.,   and   Nicoll,   H.   K.      "Complement 

Fixation  in  the  Diagnosis  of  Gonococcal  Infections." 
Jour.  Inf.  Dis.,  1915,  XVI,  303. 

38.  Pearce,  Richard  M.     "The  Scientific  Basis  of  Vaccine 

Therapy."    The  Jour.  A.M.  A.,  1913,  LXI,  2115. 

39.  Smith,  Theobald.     "An  Attempt  to  Interpret  Present- 

Day  Uses  of  Vaccine."  The  Jour.  A.  M.  A.,  1913, 
LX,  1591. 
.  "Theobald  Smith  and  Phenomena"  (Anaphylaxis).  Re- 
ferred to  by  many  experimental  workers.  See  Jour. 
A.  M.  A.,  1906,  1910,  and  Lewis,  P.  A.,  Jour.  Exper. 
Med.,  1908,  X,  1. 

40.  Babcock,  Robt.  H.     "Chronic  Cholecystitis  as  a  Cause 

of  Myocardial  Incompetence."  Jour.  A.  M.  A., 
1909,  LII,  1904. 

41.  Nichols,    Edward    H.,     and    Richardson,    Frank    L. 

"Arthritis  Deformans."  Jour.  Med.  Research,  1909,' 
N.  S.,  XVI,  149. 

42.  Weil,  Richard.    "Anaphylaxis  and  Its  Relation  to  Prob- 

lems of  Human  Disease."  Cirm.  Lancet  Clinic,  1913, 
Nov.  19. 

.  "Studies  in  Anaphylaxis.  Desensitization ;  Its  Theoreti- 
cal and  Practical  Significance."  The  Jour,  of  Med. 
Research,  1913,  New  Series,  XXIV,  233. 

.     "Studies  in  Anaphylaxis."     The  Jour.  Med.  Research, 

1914,  New  Series,  XXV,  299. 

43.  von  Pirquet,  C.  E.     "Allergy."    Arch.  Int.  Med.,  1911, 

VII,  259. 

44.  Rosenau,  M.  L.,  and  Anderson,  John  F.     "Hypersus- 

ceptibility."     Jour.  A.  M.  A.,  1906,  XL VII,  1007. 


BIBLIOGRAPHY  165 

Rosenau,  M.  L.,  and  Anderson,  John  F.  "A  Study  of  the 
Cause  of  Sudden  Death,  Following  the  Injection  of 
Horse  Serum."  1906,  Hygienic  Laboratory  Bui., 
No.  29. 

.    "Studies  on  Hypersusceptibility  and  Immunity."     1907, 

Hygienic  Laboratory  Bui.,  No.  36. 

.  "Further  Studies  Upon  the  Phenomenon  of  Anaphy- 
laxis."    1909,  Hygienic  Laboratory  Bui.,  No.  50. 

45.  Vaughan,  V.  C.     "Protein  Split  Products  in  Relation  to 

Immunity  and  Disease."  Lea  &  Febiger,  Philadel- 
phia, 1913. 

46.  Auee,   J.,   and  Lewis,   Paul  L.      "Acute   Anaphylactic 

Death  in  Guinea  Pigs."  Jour.  A.M.  A.,  1909,  LIII, 
458,  and  Jour.  Exper.  Med.,  1910,  XII,  151. 

47.  Park,  W.  H.     "A  Critical  Study  of  the  Results  of  Serum 

Therapy  in  the  Diseases  of  Man."  The  Harvey  Lec- 
tures, 1905-6,  101,  Lippincott. 

48.  Jobling,  James  W.,  and  Petersen.     "Bacterio  Therapy 

in  Typhoid  Fever."  Jour.  A.  M.  A.,  1915,  LXV, 
515. 

49.  Gay,  Frederick  P.,  and  Checkering,  Henry  T.    "Treat- 

ment of  Typhoid  Fever  by  Intravenous  Injections  of 
Polyvalent  Sensitized  Typhoid  Vaccine  Sediment." 
The  Arch,  of  Int.  Med.,  1916,  XVII,  303. 

50.  Hastings,  T.  W.   "Complement  Fixation  Tests  in  Chronic 

Infective  Deforming  Arthritis  and  Arthritis  De- 
formans."   Jour.  Exper.  Med.,  1914,  XX,  52. 

.     "Concerning  a  Polyvalent  Antigen  for  the  Complement 

Fixation  Test  for  Streptococcus  Viridans  Infection." 
Jour.  Exper.  Med.,  1914,  XX,  72. 

51.  Phillips,  Llewellyn.     "Emetine  in  Amebiasis."     Jour. 

Trop.  Med.  and  Hygiene,  1914,  Aug.  15. 

52.  Meltzer,  S.  J.     "Bronchial  Asthma  as  a  Phenomenon  of 

Anaphylaxis."    Jour.  A.  M.  A.,  1910,  LV,  1021. 

53.  Jobling,  J.  W.,  Petersen,  W.  F.,  and  Eggstein,  A.  A. 

"The  Mechanism  of  Anaphylactic   Shock.      Studies 


166  BIBLIOGRAPHY 

on  Ferment  Action."    Jour.  Exper.  Med.,  1914,  XX, 
401,  and  1915,  XXII,  401. 

54.  Klotz,    Oskar.       "Experimental    Bacterial    Interstitial 

Nephritis."       Trans.    Assoc.    American    Physicians, 
1914,  XXIX,  49. 

55.  Ophuls,  W.     "Subacute  and  Chronic  Nephritis  as  Found 

In  One  Thousand  Unselected  Autopsies."     Arch.  Int. 
Med.,  1912,  IX,  156. 

56.  Sippy,  B.   W.      "Gastric   and  Duodenal  Ulcer,   Medical 

Care  by  an  Efficient  Removal  of  Gastric  Juice  Cor- 
rosion."   Jour.  A.  M.  A.,  1915,  LXIV,  1623. 

57.  Thayer,  W.  S.     "On  Gonorrheal  Septicemia  and  Endo- 

carditis."    Amer.  Jour.  Med.  Sci.,  Nov.,  1905,  new 
series,  CXXXI,  751. 

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